International Journal of Molecular Sciences

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Open AccessEditorial

Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules

by Anne Vejux

Int. J. Mol. Sci. 2023, 24(14), 11465; https://doi.org/10.3390/ijms241411465 - 14 Jul 2023

Viewed by 970

Abstract

A neurodegenerative disease is a pathological condition affecting neurons, condemning them to death [...] Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

Research

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14 pages, 1782 KiB

Open AccessArticle

β-Naphthoflavone and Ethanol Reverse Mitochondrial Dysfunction in A Parkinsonian Model of Neurodegeneration

by Jesus Fernandez-Abascal, Elda Chiaino, Maria Frosini, Gavin P. Davey and Massimo Valoti

Int. J. Mol. Sci. 2020, 21(11), 3955; https://doi.org/10.3390/ijms21113955 - 31 May 2020

Cited by 7 | Viewed by 2802

Abstract

The 1-methyl-4-phenylpyridinium (MPP⁺) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the [...] Read more.

The 1-methyl-4-phenylpyridinium (MPP⁺) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the development of this neurodegenerative disease. In order to study a possible role for CYP induction in neurorepair, we designed an in vitro model where undifferentiated neuroblastoma SH-SY5Y cells were treated with the CYP inducers β-naphthoflavone (βNF) and ethanol (EtOH) before and during exposure to the parkinsonian neurotoxin, MPP⁺. The toxic effect of MPP⁺ in cell viability was rescued with both βNF and EtOH treatments. We also report that this was due to a decrease in reactive oxygen species (ROS) production, restoration of mitochondrial fusion kinetics, and mitochondrial membrane potential. These treatments also protected complex I activity against the inhibitory effects caused by MPP⁺, suggesting a possible neuroprotective role for CYP inducers. These results bring new insights into the possible role of CYP isoenzymes in xenobiotic clearance and central nervous system homeostasis. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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20 pages, 3014 KiB

Open AccessArticle

An α5 GABAA Receptor Inverse Agonist, α5IA, Attenuates Amyloid Beta-Induced Neuronal Death in Mouse Hippocampal Cultures

by Chitra Vinnakota, Karan Govindpani, Warren Perry Tate, Katie Peppercorn, Praju Vikas Anekal, Henry John Waldvogel, Richard Lewis Maxwell Faull and Andrea Kwakowsky

Int. J. Mol. Sci. 2020, 21(9), 3284; https://doi.org/10.3390/ijms21093284 - 6 May 2020

Cited by 9 | Viewed by 4108

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which no cognition-restoring therapies exist. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Increasing evidence suggests a remodeling of the GABAergic system in AD, which might represent an important therapeutic target. [...] Read more.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which no cognition-restoring therapies exist. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Increasing evidence suggests a remodeling of the GABAergic system in AD, which might represent an important therapeutic target. An inverse agonist of α5 subunit-containing GABAA receptors (α5GABAARs), 3-(5-Methylisoxazol-3-yl)-6-[(1-methyl-1,2,3-triazol-4-yl)methyloxy]-1,2,4-triazolo[3–a]phthalazine (α5IA) has cognition-enhancing properties. This study aimed to characterize the effects of α5IA on amyloid beta (Aβ_1–42)-induced molecular and cellular changes. Mouse primary hippocampal cultures were exposed to either Aβ_1-42 alone, or α5IA alone, α5IA with Aβ_1–42 or vehicle alone, and changes in cell viability and mRNA expression of several GABAergic signaling components were assessed. Treatment with 100 nM of α5IA reduced Aβ_1–42-induced cell loss by 23.8% (p < 0.0001) after 6 h and by 17.3% after 5 days of treatment (p < 0.0001). Furthermore, we observed an Aβ_1-42-induced increase in ambient GABA levels, as well as upregulated mRNA expression of the GABAAR α2,α5,β2/3 subunits and the GABABR R1 and R2 subunits. Such changes in GABARs expression could potentially disrupt inhibitory neurotransmission and normal network activity. Treatment with α5IA restored Aβ_1-42-induced changes in the expression of α5GABAARs. In summary, this compound might hold neuroprotective potential and represent a new therapeutic avenue for AD. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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19 pages, 2831 KiB

Open AccessArticle

Transcriptomic and Network Analysis Identifies Shared and Unique Pathways across Dementia Spectrum Disorders

by Jose A. Santiago, Virginie Bottero and Judith A. Potashkin

Int. J. Mol. Sci. 2020, 21(6), 2050; https://doi.org/10.3390/ijms21062050 - 17 Mar 2020

Cited by 17 | Viewed by 4349

Abstract

Background: Dementia is a growing public health concern with an estimated prevalence of 50 million people worldwide. Alzheimer’s disease (AD) and vascular and frontotemporal dementias (VaD, FTD), share many clinical, genetical, and pathological features making the diagnosis difficult. Methods: In this study, we [...] Read more.

Background: Dementia is a growing public health concern with an estimated prevalence of 50 million people worldwide. Alzheimer’s disease (AD) and vascular and frontotemporal dementias (VaD, FTD), share many clinical, genetical, and pathological features making the diagnosis difficult. Methods: In this study, we compared the transcriptome from the frontal cortex of patients with AD, VaD, and FTD to identify dysregulated pathways. Results: Upregulated genes in AD were enriched in adherens and tight junctions, mitogen-activated protein kinase, and phosphatidylinositol 3-kinase and protein kinase B/Akt signaling pathways, whereas downregulated genes associated with calcium signaling. Upregulated genes in VaD were centered on infectious diseases and nuclear factor kappa beta signaling, whereas downregulated genes are involved in biosynthesis of amino acids and the pentose phosphate pathway. Upregulated genes in FTD were associated with ECM receptor interactions and the lysosome, whereas downregulated genes were involved in glutamatergic synapse and MAPK signaling. The transcription factor KFL4 was shared among the 3 types of dementia. Conclusions: Collectively, we identified similarities and differences in dysregulated pathways and transcription factors among the dementias. The shared pathways and transcription factors may indicate a potential common etiology, whereas the differences may be useful for distinguishing dementias. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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21 pages, 3863 KiB

Open AccessArticle

Differential Expression of miRNAs and Behavioral Change in the Cuprizone-Induced Demyelination Mouse Model

by Seung Ro Han, Yun Hee Kang, Hyungtaek Jeon, Suhyuk Lee, Sang-Jin Park, Dae-Yong Song, Sun Seek Min, Seung-Min Yoo, Myung-Shin Lee and Seung-Hoon Lee

Int. J. Mol. Sci. 2020, 21(2), 646; https://doi.org/10.3390/ijms21020646 - 18 Jan 2020

Cited by 21 | Viewed by 4837

Abstract

The demyelinating diseases of the central nervous system involve myelin abnormalities, oligodendrocyte damage, and consequent glia activation. Neurotoxicant cuprizone (CPZ) was used to establish a mouse model of demyelination. However, the effects of CPZ on microRNA (miRNA) expression and behavior have not been [...] Read more.

The demyelinating diseases of the central nervous system involve myelin abnormalities, oligodendrocyte damage, and consequent glia activation. Neurotoxicant cuprizone (CPZ) was used to establish a mouse model of demyelination. However, the effects of CPZ on microRNA (miRNA) expression and behavior have not been clearly reported. We analyzed the behavior of mice administered a diet containing 0.2% CPZ for 6 weeks, followed by 6 weeks of recovery. Rotarod analysis demonstrated that the treated group had poorer motor coordination than control animals. This effect was reversed after 6 weeks of CPZ withdrawal. Open-field tests showed that CPZ-treated mice exhibited significantly increased anxiety and decreased exploratory behavior. CPZ-induced demyelination was observed to be alleviated after 4 weeks of CPZ treatment, according to luxol fast blue (LFB) staining and myelin basic protein (MBP) expression. miRNA expression profiling showed that the expression of 240 miRNAs was significantly changed in CPZ-fed mice compared with controls. Furthermore, miR-155-5p and miR-20a-5p upregulations enhanced NgR induction through Smad 2 and Smad 4 suppression in demyelination. Taken together, our results demonstrate that CPZ-mediated demyelination induces behavioral deficits with apparent alterations in miRNA expression, suggesting that differences in miRNA expression in vivo may be new potential therapeutic targets for remyelination. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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9 pages, 1074 KiB

Open AccessArticle

Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model

by Thomas Nury, Margaux Doria, Gérard Lizard and Anne Vejux

Int. J. Mol. Sci. 2020, 21(2), 641; https://doi.org/10.3390/ijms21020641 - 18 Jan 2020

Cited by 11 | Viewed by 3444

Abstract

In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to [...] Read more.

In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50 µM) on very long-chain fatty acid-induced toxicity was studied by several complementary methods: phase contrast microscopy to evaluate cell viability and morphology, the MTT test to monitor the impact on mitochondrial function, propidium iodide staining to study plasma membrane integrity, and DHE staining to measure oxidative stress. A Western blot assay was used to assess autophagy through modification of LC3 protein. The various experiments were carried out on the cellular model of 158N murine oligodendrocytes. In 158N cells, our data establish that DHA is able to inhibit all tested cytotoxic effects induced by very long-chain fatty acids. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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13 pages, 3618 KiB

Open AccessArticle

Mechanisms of Neuronal Death in the Cerebral Cortex during Aging and Development of Alzheimer’s Disease-Like Pathology in Rats

by Darya V. Telegina, Gleb K. Suvorov, Oyuna S. Kozhevnikova and Nataliya G. Kolosova

Int. J. Mol. Sci. 2019, 20(22), 5632; https://doi.org/10.3390/ijms20225632 - 11 Nov 2019

Cited by 31 | Viewed by 4265

Abstract

Alzheimer’s disease (AD) is the commonest type of late-life dementia and damages the cerebral cortex, a vulnerable brain region implicated in memory, emotion, cognition, and decision-making behavior. AD is characterized by progressive neuronal loss, but the mechanisms of cell death at different stages [...] Read more.

Alzheimer’s disease (AD) is the commonest type of late-life dementia and damages the cerebral cortex, a vulnerable brain region implicated in memory, emotion, cognition, and decision-making behavior. AD is characterized by progressive neuronal loss, but the mechanisms of cell death at different stages of the disease remain unknown. Here, by means of OXYS rats as an appropriate model of the most common (sporadic) AD form, we studied the main pathways of cell death during development of AD-like pathology, including the preclinical stage. We found that apoptosis is activated at the pre-symptomatic stage (age 20 days) correlating with the retardation of brain development in the OXYS strain early in life. Progression of the AD-like pathology was accompanied by activation of apoptosis and necroptosis resulting from a decline of autophagy-mediated proteostasis. Our results are consistent with the idea that the nature of changes in the pathways of apoptosis, autophagy, and necrosis depends on the stage of AD. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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13 pages, 2395 KiB

Open AccessArticle

Nimodipine-Dependent Protection of Schwann Cells, Astrocytes and Neuronal Cells from Osmotic, Oxidative and Heat Stress Is Associated with the Activation of AKT and CREB

by Sandra Leisz, Sebastian Simmermacher, Julian Prell, Christian Strauss and Christian Scheller

Int. J. Mol. Sci. 2019, 20(18), 4578; https://doi.org/10.3390/ijms20184578 - 16 Sep 2019

Cited by 23 | Viewed by 4192

Abstract

Clinical and experimental data assumed a neuroprotective effect of the calcium channel blocker nimodipine. However, it has not been proven which neuronal or glial cell types are affected by nimodipine and which mechanisms underlie these neuroprotective effects. Therefore, the aim of this study [...] Read more.

Clinical and experimental data assumed a neuroprotective effect of the calcium channel blocker nimodipine. However, it has not been proven which neuronal or glial cell types are affected by nimodipine and which mechanisms underlie these neuroprotective effects. Therefore, the aim of this study was to investigate the influence of nimodipine treatment on the in vitro neurotoxicity of different cell types in various stress models and to identify the associated molecular mechanisms. Therefore, cell lines from Schwann cells, neuronal cells and astrocytes were pretreated for 24 h with nimodipine and incubated under stress conditions such as osmotic, oxidative and heat stress. The cytotoxicity was measured via the lactate dehydrogenase (LDH) activity of cell culture supernatant. As a result, the nimodipine treatment led to a statistically significantly reduced cytotoxicity in Schwann cells and neurons during osmotic (p ≤ 0.01), oxidative (p ≤ 0.001) and heat stress (p ≤ 0.05), when compared to the vehicle. The cytotoxicity of astrocytes was nimodipine-dependently reduced during osmotic (p ≤ 0.01), oxidative (p ≤ 0.001) and heat stress (not significant). Moreover, a decreased caspase activity as well as an increased proteinkinase B (AKT) and cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation could be observed after the nimodipine treatment under different stress conditions. These results demonstrate a cell type-independent neuroprotective effect of the prophylactic nimodipine treatment, which is associated with the prevention of stress-dependent apoptosis through the activation of CREB and AKT signaling pathways and the reduction of caspase 3 activity. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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Review

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17 pages, 675 KiB

Open AccessReview

Metal Imbalance in Neurodegenerative Diseases with a Specific Concern to the Brain of Multiple Sclerosis Patients

by Jean-Philippe Dales and Sophie Desplat-Jégo

Int. J. Mol. Sci. 2020, 21(23), 9105; https://doi.org/10.3390/ijms21239105 - 30 Nov 2020

Cited by 23 | Viewed by 4012

Abstract

There is increasing evidence that deregulation of metals contributes to a vast range of neurodegenerative diseases including multiple sclerosis (MS). MS is a chronic inflammatory disease of the central nervous system (CNS) manifesting disability and neurological symptoms. The precise origin of MS is [...] Read more.

There is increasing evidence that deregulation of metals contributes to a vast range of neurodegenerative diseases including multiple sclerosis (MS). MS is a chronic inflammatory disease of the central nervous system (CNS) manifesting disability and neurological symptoms. The precise origin of MS is unknown, but the disease is characterized by focal inflammatory lesions in the CNS associated with an autoimmune reaction against myelin. The treatment of this disease has mainly been based on the prescription of immunosuppressive and immune-modulating agents. However, the rate of progressive disability and early mortality is still worrisome. Metals may represent new diagnostic and predictive markers of severity and disability as well as innovative candidate drug targets for future therapies. In this review, we describe the recent advances in our understanding on the role of metals in brain disorders of neurodegenerative diseases and MS patients. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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30 pages, 5732 KiB

Open AccessReview

Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases

by Fang Luo, Aaron F. Sandhu, Wiramon Rungratanawanich, George E. Williams, Mohammed Akbar, Shuanhu Zhou, Byoung-Joon Song and Xin Wang

Int. J. Mol. Sci. 2020, 21(19), 7174; https://doi.org/10.3390/ijms21197174 - 28 Sep 2020

Cited by 109 | Viewed by 12558

Abstract

With aging, the nervous system gradually undergoes degeneration. Increased oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and cell death are considered to be common pathophysiological mechanisms of various neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), organophosphate-induced [...] Read more.

With aging, the nervous system gradually undergoes degeneration. Increased oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and cell death are considered to be common pathophysiological mechanisms of various neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), organophosphate-induced delayed neuropathy (OPIDN), and amyotrophic lateral sclerosis (ALS). Autophagy is a cellular basic metabolic process that degrades the aggregated or misfolded proteins and abnormal organelles in cells. The abnormal regulation of neuronal autophagy is accompanied by the accumulation and deposition of irregular proteins, leading to changes in neuron homeostasis and neurodegeneration. Autophagy exhibits both a protective mechanism and a damage pathway related to programmed cell death. Because of its “double-edged sword”, autophagy plays an important role in neurological damage and NDDs including AD, PD, HD, OPIDN, and ALS. Melatonin is a neuroendocrine hormone mainly synthesized in the pineal gland and exhibits a wide range of biological functions, such as sleep control, regulating circadian rhythm, immune enhancement, metabolism regulation, antioxidant, anti-aging, and anti-tumor effects. It can prevent cell death, reduce inflammation, block calcium channels, etc. In this review, we briefly discuss the neuroprotective role of melatonin against various NDDs via regulating autophagy, which could be a new field for future translational research and clinical studies to discover preventive or therapeutic agents for many NDDs. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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16 pages, 827 KiB

Open AccessReview

Participation of Amyloid and Tau Protein in Neuronal Death and Neurodegeneration after Brain Ischemia

by Ryszard Pluta, Marzena Ułamek-Kozioł, Sławomir Januszewski and Stanisław J. Czuczwar

Int. J. Mol. Sci. 2020, 21(13), 4599; https://doi.org/10.3390/ijms21134599 - 28 Jun 2020

Cited by 23 | Viewed by 2713

Abstract

Current evidence indicates that postischemic brain injury is associated with the accumulation of folding proteins, such as amyloid and tau protein, in the intra- and extracellular spaces of neuronal cells. In this review, we summarize protein changes associated with Alzheimer’s disease and their [...] Read more.

Current evidence indicates that postischemic brain injury is associated with the accumulation of folding proteins, such as amyloid and tau protein, in the intra- and extracellular spaces of neuronal cells. In this review, we summarize protein changes associated with Alzheimer’s disease and their gene expression (amyloid protein precursor and tau protein) after brain ischemia, and their roles in the postischemic period. Recent advances in understanding the postischemic mechanisms in development of neurodegeneration have revealed dysregulation of amyloid protein precursor, α-, β- and γ-secretase and tau protein genes. Reduced expression of the α-secretase gene after brain ischemia with recirculation causes neuronal cells to be less resistant to injury. We present the latest data that Alzheimer’s disease-related proteins and their genes play a crucial role in postischemic neurodegeneration. Understanding the underlying processes of linking Alzheimer’s disease-related proteins and their genes in development of postischemic neurodegeneration will provide the most significant goals to date for therapeutic development. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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17 pages, 1167 KiB

Open AccessReview

The Potential for Natural Antioxidant Supplementation in the Early Stages of Neurodegenerative Disorders

by Francesca Oppedisano, Jessica Maiuolo, Micaela Gliozzi, Vincenzo Musolino, Cristina Carresi, Saverio Nucera, Miriam Scicchitano, Federica Scarano, Francesca Bosco, Roberta Macrì, Stefano Ruga, Maria Caterina Zito, Ernesto Palma, Carolina Muscoli and Vincenzo Mollace

Int. J. Mol. Sci. 2020, 21(7), 2618; https://doi.org/10.3390/ijms21072618 - 9 Apr 2020

Cited by 39 | Viewed by 4430

Abstract

The neurodegenerative process is characterized by the progressive ultrastructural alterations of selected classes of neurons accompanied by imbalanced cellular homeostasis, a process which culminates, in the later stages, in cell death and the loss of specific neurological functions. Apart from the neuronal cell [...] Read more.

The neurodegenerative process is characterized by the progressive ultrastructural alterations of selected classes of neurons accompanied by imbalanced cellular homeostasis, a process which culminates, in the later stages, in cell death and the loss of specific neurological functions. Apart from the neuronal cell impairment in selected areas of the central nervous system which characterizes many neurodegenerative diseases (e.g., Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, etc.), some alterations may be found in the early stages including gliosis and the misfolding or unfolding accumulation of proteins. On the other hand, several common pathophysiological mechanisms can be found early in the course of the disease including altered oxidative metabolism, the loss of cross-talk among the cellular organelles and increased neuroinflammation. Thus, antioxidant compounds have been suggested, in recent years, as a potential strategy for preventing or counteracting neuronal cell death and nutraceutical supplementation has been studied in approaching the early phases of neurodegenerative diseases. The present review will deal with the pathophysiological mechanisms underlying the early stages of the neurodegenerative process. In addition, the potential of nutraceutical supplementation in counteracting these diseases will be assessed. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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19 pages, 1303 KiB

Open AccessReview

Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection

by Thomas Nury, Gérard Lizard and Anne Vejux

Int. J. Mol. Sci. 2020, 21(7), 2501; https://doi.org/10.3390/ijms21072501 - 3 Apr 2020

Cited by 13 | Viewed by 5492

Abstract

Neurodegenerative diseases, particularly Parkinson’s and Alzheimer’s, have common features: protein accumulation, cell death with mitochondrial involvement and oxidative stress. Patients are treated to cure the symptoms, but the treatments do not target the causes; so, the disease is not stopped. It is interesting [...] Read more.

Neurodegenerative diseases, particularly Parkinson’s and Alzheimer’s, have common features: protein accumulation, cell death with mitochondrial involvement and oxidative stress. Patients are treated to cure the symptoms, but the treatments do not target the causes; so, the disease is not stopped. It is interesting to look at the side of nutrition which could help prevent the first signs of the disease or slow its progression in addition to existing therapeutic strategies. Lipids, whether in the form of vegetable or animal oils or in the form of fatty acids, could be incorporated into diets with the aim of preventing neurodegenerative diseases. These different lipids can inhibit the cytotoxicity induced during the pathology, whether at the level of mitochondria, oxidative stress or apoptosis and inflammation. The conclusions of the various studies cited are oriented towards the preventive use of oils or fatty acids. The future of these lipids that can be used in therapy/prevention will undoubtedly involve a better delivery to the body and to the brain by utilizing lipid encapsulation. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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21 pages, 706 KiB

Open AccessReview

Role of Alcohol Drinking in Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

by Bin Peng, Qiang Yang, Rachna B Joshi, Yuancai Liu, Mohammed Akbar, Byoung-Joon Song, Shuanhu Zhou and Xin Wang

Int. J. Mol. Sci. 2020, 21(7), 2316; https://doi.org/10.3390/ijms21072316 - 27 Mar 2020

Cited by 85 | Viewed by 19359

Abstract

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), increase as the population ages around the world. Environmental factors also play an important role in most cases. Alcohol consumption exists extensively and it acts as one of the [...] Read more.

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), increase as the population ages around the world. Environmental factors also play an important role in most cases. Alcohol consumption exists extensively and it acts as one of the environmental factors that promotes these neurodegenerative diseases. The brain is a major target for the actions of alcohol, and heavy alcohol consumption has long been associated with brain damage. Chronic alcohol intake leads to elevated glutamate-induced excitotoxicity, oxidative stress and permanent neuronal damage associated with malnutrition. The relationship and contributing mechanisms of alcohol with these three diseases are different. Epidemiological studies have reported a reduction in the prevalence of Alzheimer’s disease in individuals who drink low amounts of alcohol; low or moderate concentrations of ethanol protect against β-amyloid (Aβ) toxicity in hippocampal neurons; and excessive amounts of ethanol increase accumulation of Aβ and Tau phosphorylation. Alcohol has been suggested to be either protective of, or not associated with, PD. However, experimental animal studies indicate that chronic heavy alcohol consumption may have dopamine neurotoxic effects through the induction of Cytochrome P450 2E1 (CYP2E1) and an increase in the amount of α-Synuclein (αSYN) relevant to PD. The findings on the association between alcohol consumption and ALS are inconsistent; a recent population-based study suggests that alcohol drinking seems to not influence the risk of developing ALS. Additional research is needed to clarify the potential etiological involvement of alcohol intake in causing or resulting in major neurodegenerative diseases, which will eventually lead to potential therapeutics against these alcoholic neurodegenerative diseases. Full article

(This article belongs to the Special Issue Cell Death and Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules)

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