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Molecular Mechanism in Neurodegeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 September 2024 | Viewed by 1961

Special Issue Editors


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Guest Editor
Department of Biology, Medical University of Pleven, 5800 Pleven, Bulgaria
Interests: neuroscience; neuropharmacology; molecular markers of oxidative stress; models of neurodegenerative diseases; aging

Special Issue Information

Dear Colleagues,

Neurodegeneration refers to the progressive loss of structure or function of neurons, leading to a decline in cognitive and motor functions. Several diseases are characterized by neurodegeneration, and while each disease has its unique features, there are some common pathogenic mechanisms that contribute to the degeneration of neurons across different conditions. Here are some specific and common mechanisms underlying neurodegeneration:

(1) Protein Misfolding and Aggregation: Alzheimer's Disease (AD) (Amyloid-beta (Aβ) and tau proteins misfold and aggregate, forming plaques and neurofibrillary tangles); Parkinson's Disease (PD): (Alpha-synuclein misfolds and forms Lewy bodies. (2) Mitochondrial Dysfunction: Dysfunction in the energy-producing mitochondria is a common feature in many neurodegenerative diseases. Amyotrophic Lateral Sclerosis (ALS): Impaired mitochondrial function contributes to motor neuron degeneration. (3) Oxidative Stress: Free radicals and reactive oxygen species (ROS) damage cellular components, leading to neurodegeneration. Huntington's Disease (HD): Oxidative stress plays a role in the pathology of HD. (4) Inflammation: Chronic inflammation in the brain contributes to neuronal damage. Multiple Sclerosis (MS): Inflammatory processes result in demyelination and axonal damage. (5) Excitotoxicity: Overactivation of glutamate receptors leads to excessive influx of calcium ions, damaging neurons. Amyotrophic Lateral Sclerosis (ALS): Excitotoxicity contributes to motor neuron degeneration. (6) Genetic Factors: Mutations in specific genes contribute to the susceptibility or causation of neurodegenerative diseases. Frontotemporal Dementia (FTD): Mutations in genes such as C9orf72 are associated with FTD. (7) Impaired Autophagy and Proteasomal Dysfunction: Inefficient removal of damaged proteins and organelles contributes to the accumulation of toxic materials. Parkinson's Disease (PD): Impaired autophagy is implicated in the accumulation of alpha-synuclein. (8) Neuroinflammation: Activation of immune cells in the central nervous system contributes to neurodegeneration. Alzheimer's Disease (AD): Neuroinflammation is a characteristic feature of AD. (9) Vascular Dysfunction:

Impaired blood flow and vascular health contribute to neuronal damage. Vascular Dementia: Neurodegeneration is linked to vascular problems in the brain.

Understanding these common mechanisms helps researchers develop therapeutic strategies that target multiple diseases or pathways simultaneously. However, it is essential to consider the unique aspects of each neurodegenerative disorder for effective treatment approaches.

Therefore, this Special Issue invites the submission of research manuscripts, reviews, as well as short commentaries on topics related to the underlying mechanism and the role of specific or common signaling involved in the pathogenesis of neurodegenerative diseases. Submissions can cover reports from animal models to clinical studies in the field of neurodegenerative diseases.

Dr. Milena Atanasova
Dr. Jana Tchekalarova
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • abnormal protein dynamics with misfolding
  • defective degradation
  • proteasomal dysfunction and aggregation
  • often with actions and mutations of molecular chaperones
  • oxidative stress (OS) and formation of free radicals/reactive oxygen species (ROS)

Published Papers (3 papers)

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Research

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23 pages, 6575 KiB  
Article
Protective Effect of Arzanol against H2O2-Induced Oxidative Stress Damage in Differentiated and Undifferentiated SH-SY5Y Cells
by Franca Piras, Valeria Sogos, Federica Pollastro and Antonella Rosa
Int. J. Mol. Sci. 2024, 25(13), 7386; https://doi.org/10.3390/ijms25137386 - 5 Jul 2024
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Abstract
Oxidative stress can damage neuronal cells, greatly contributing to neurodegenerative diseases (NDs). In this study, the protective activity of arzanol, a natural prenylated α-pyrone-phloroglucinol heterodimer, was evaluated against the H2O2-induced oxidative damage in trans-retinoic acid-differentiated (neuron-like) human SH-SY5Y cells, [...] Read more.
Oxidative stress can damage neuronal cells, greatly contributing to neurodegenerative diseases (NDs). In this study, the protective activity of arzanol, a natural prenylated α-pyrone-phloroglucinol heterodimer, was evaluated against the H2O2-induced oxidative damage in trans-retinoic acid-differentiated (neuron-like) human SH-SY5Y cells, widely used as a neuronal cell model of neurological disorders. The pre-incubation (for 2 and 24 h) with arzanol (5, 10, and 25 μM) significantly preserved differentiated SH-SY5Y cells from cytotoxicity (MTT assay) and morphological changes induced by 0.25 and 0.5 mM H2O2. Arzanol reduced the generation of reactive oxygen species (ROS) induced by 2 h oxidation with H2O2 0.5 mM, established by 2′,7′-dichlorodihydrofluorescein diacetate assay. The 2 h incubation of differentiated SH-SY5Y cells with H2O2 determined a significant increase in the number of apoptotic cells versus control cells, evaluated by propidium iodide fluorescence assay (red fluorescence) and NucView® 488 assay (green fluorescence). Arzanol pre-treatment (2 h) exerted a noteworthy significant protective effect against apoptosis. In addition, arzanol was tested, for comparison, in undifferentiated SH-SY5Y cells for cytotoxicity and its ability to protect against H2O2-induced oxidative stress. Furthermore, the PubChem database and freely accessible web tools SwissADME and pkCSM-pharmacokinetics were used to assess the physicochemical and pharmacokinetic properties of arzanol. Our results qualify arzanol as an antioxidant agent with potential neuroprotective effects against neuronal oxidative stress implicated in NDs. Full article
(This article belongs to the Special Issue Molecular Mechanism in Neurodegeneration)
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18 pages, 2907 KiB  
Article
Protective Effect of the Novel Melatonin Analogue Containing Donepezil Fragment on Memory Impairment via MT/ERK/CREB Signaling in the Hippocampus in a Rat Model of Pinealectomy and Subsequent Aβ1-42 Infusion
by Jana Tchekalarova, Petya Ivanova, Desislava Krushovlieva, Lidia Kortenska and Violina T. Angelova
Int. J. Mol. Sci. 2024, 25(3), 1867; https://doi.org/10.3390/ijms25031867 - 3 Feb 2024
Cited by 1 | Viewed by 861
Abstract
A reduction in melatonin function contributes to the acceleration of Alzheimer’s disease (AD), and understanding the molecular processes of melatonin-related signaling is critical for intervention in AD progression. Recently, we synthesized a series of melatonin analogues with donepezil fragments and tested them in [...] Read more.
A reduction in melatonin function contributes to the acceleration of Alzheimer’s disease (AD), and understanding the molecular processes of melatonin-related signaling is critical for intervention in AD progression. Recently, we synthesized a series of melatonin analogues with donepezil fragments and tested them in silico and in vitro. In this study, one of the most potent compounds, 3c, was evaluated in a rat model of pinealectomy (pin) followed by icvAβ1-42 infusion. Melatonin was used as the reference drug. Treatment with melatonin and 3c (10 mg/kg, i.p. for 14 days) had a beneficial effect on memory decline and the concomitant increase in hippocampal Aβ1-42 and pTAU in the pin+icvAβ1-42 rats. Melatonin supplementation facilitated non-amyloidogenic signaling via non-receptor (histone deacetylase sirtuin 1, SIRT1) and receptor-related signaling (MT/ERK/CREB). The hybrid 3c analogue up-regulated the MT1A and MT2B receptors, pERK and pCREB. Our results strongly support the hypothesis that melatonin-related analogues may become a promising drug candidate for Alzheimer’s disease therapy. Full article
(This article belongs to the Special Issue Molecular Mechanism in Neurodegeneration)
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Review

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19 pages, 2302 KiB  
Review
Current View on PPAR-α and Its Relation to Neurosteroids in Alzheimer’s Disease and Other Neuropsychiatric Disorders: Promising Targets in a Therapeutic Strategy
by Sylwia Żulińska, Anna K. Strosznajder and Joanna B. Strosznajder
Int. J. Mol. Sci. 2024, 25(13), 7106; https://doi.org/10.3390/ijms25137106 - 28 Jun 2024
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Abstract
Peroxisome proliferator-activated receptors (PPARs) may play an important role in the pathomechanism/pathogenesis of Alzheimer’s disease (AD) and several other neurological/neuropsychiatric disorders. AD leads to progressive alterations in the redox state, ion homeostasis, lipids, and protein metabolism. Significant alterations in molecular processes and the [...] Read more.
Peroxisome proliferator-activated receptors (PPARs) may play an important role in the pathomechanism/pathogenesis of Alzheimer’s disease (AD) and several other neurological/neuropsychiatric disorders. AD leads to progressive alterations in the redox state, ion homeostasis, lipids, and protein metabolism. Significant alterations in molecular processes and the functioning of several signaling pathways result in the degeneration and death of synapses and neuronal cells, leading to the most severe dementia. Peroxisome proliferator-activated receptor alpha (PPAR-α) is among the processes affected by AD; it regulates the transcription of genes related to the metabolism of cholesterol, fatty acids, other lipids and neurotransmission, mitochondria biogenesis, and function. PPAR-α is involved in the cholesterol transport to mitochondria, the substrate for neurosteroid biosynthesis. PPAR-α-coding enzymes, such as sulfotransferases, which are responsible for neurosteroid sulfation. The relation between PPAR-α and cholesterol/neurosteroids may have a significant impact on the course and progression of neurodegeneration/neuroprotection processes. Unfortunately, despite many years of intensive studies, the pathogenesis of AD is unknown and therapy for AD and other neurodegenerative diseases is symptomatic, presenting a significant goal and challenge today. This review presents recent achievements in therapeutic approaches for AD, which are targeting PPAR-α and its relation to cholesterol and neurosteroids in AD and neuropsychiatric disorders. Full article
(This article belongs to the Special Issue Molecular Mechanism in Neurodegeneration)
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