Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular Mechanisms and Therapeutics of Parkinson's Disease 2022

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (18 August 2023) | Viewed by 10133

Share This Special Issue

Special Issue Editor

Dr. Demetrios K. Vassilatis

E-Mail Website
Guest Editor

Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Street, 11527 Athens, Greece
Interests: Parkinson’s disease; neuroprotection; neurodegeneration; drug design; molecular medicine

Special Issue Information

Dear Colleagues,

Parkinson's Disease (PD) is characterized by the progressive degeneration of dopaminergic neurons (DA-neurons) and the gradual depletion of dopamine (DA). Current treatments replenish the DA deficit and improve symptoms, but neurodegeneration continues. Neuroprotection treatments do not affect patient symptoms but aim to modulate remarkably diverse pathways and, despite intense efforts, neuroprotective therapies have not been discovered.

Deciphering the molecular mechanisms of PD pathogenesis is of paramount importance in stopping neurodegeneration. Experimental evidence and postmortem studies support the involvement of protein toxicity, mitochondrial dysfunction, and oxidative stress, as well as glial cell mediated neuroinflammation.

Even though the etiology of PD for the vast majority of cases remains unknown, genetics and association studies have revealed more than twenty loci and several environmental factors to be implicated. These discoveries have created a resurgence of research offering deeper understanding of the pathogenetic pathways and provide potential targets for novel treatments. Indeed, several new approaches are currently undergoing clinical trials, raising expectations for a cure.

This Special Issue aims to collect exciting new findings on the molecular mechanisms of PD pathogenesis, as well as on translational research of PD therapeutics. We cordially invite authors to contribute original research articles focusing on molecular, cellular, or whole organism experimental evidence helping to validate mechanisms for neuroprotection. Such experimental evidence could include, but it is not limited to:

The molecular role of genetically, or otherwise, identified factors in protein toxicity, mitochondrial dysfunction, and oxidative stress, as well as glial cell mediated neuroinflammation related to PD.
Mechanistic insights of altered expression levels due to neuroprotective or neurodegenerative interventions in preclinical models.
Biochemical or expression level adaptations during aging that predispose or protect from PD.
Molecular mechanisms leading to neuronal survival.
Mechanism of action of Pharmacological agents for PD.
Molecular or genetic manipulation (overexpression / knockdown) affecting neuroprotective or neurodegenerative outcome.

Dr. Demetrios K. Vassilatis
Guest Editor

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

Parkinson’s disease
neuroprotection
neurodegeneration
tatget validation
drug discovery
drug mode of action
neuroinflammation
molecular medicine

Published Papers (3 papers)

Download All Papers

Research

Jump to: Review

16 pages, 3568 KiB

Open AccessArticle

Inhibition of the Exocyst Complex Attenuates the LRRK2 Pathological Effects

by Cristina Ciampelli, Grazia Galleri, Silvia Puggioni, Milena Fais, Lucia Iannotta, Manuela Galioto, Marta Becciu, Elisa Greggio, Roberto Bernardoni, Claudia Crosio and Ciro Iaccarino

Int. J. Mol. Sci. 2023, 24(16), 12656; https://doi.org/10.3390/ijms241612656 - 10 Aug 2023

Viewed by 1193

Abstract

Pathological mutations in leucine-rich repeat kinase 2 (LRRK2) gene are the major genetic cause of Parkinson’s disease (PD). Multiple lines of evidence link LRRK2 to the control of vesicle dynamics through phosphorylation of a subset of RAB proteins. However, the molecular mechanisms underlying these processes are not fully elucidated. We have previously demonstrated that LRRK2 increases the exocyst complex assembly by Sec8 interaction, one of the eight members of the exocyst complex, and that Sec8 over-expression mitigates the LRRK2 pathological effect in PC12 cells. Here, we extend this analysis using LRRK2 drosophila models and show that the LRRK2-dependent exocyst complex assembly increase is downstream of RAB phosphorylation. Moreover, exocyst complex inhibition rescues mutant LRRK2 pathogenic phenotype in cellular and drosophila models. Finally, prolonged exocyst inhibition leads to a significant reduction in the LRRK2 protein level, overall supporting the role of the exocyst complex in the LRRK2 pathway. Taken together, our study suggests that modulation of the exocyst complex may represent a novel therapeutic target for PD. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Therapeutics of Parkinson's Disease 2022)

► Show Figures

Figure 1

Review

Jump to: Research

41 pages, 3154 KiB

Open AccessReview

Pathogenesis of α-Synuclein in Parkinson’s Disease: From a Neuron-Glia Crosstalk Perspective

by Shuanglong Yi, Linfang Wang, Honglei Wang, Margaret S. Ho and Shiping Zhang

Int. J. Mol. Sci. 2022, 23(23), 14753; https://doi.org/10.3390/ijms232314753 - 25 Nov 2022

Cited by 12 | Viewed by 4703

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder. The classical behavioral defects of PD patients involve motor symptoms such as bradykinesia, tremor, and rigidity, as well as non-motor symptoms such as anosmia, depression, and cognitive impairment. Pathologically, the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN) and the accumulation of α-synuclein (α-syn)-composed Lewy bodies (LBs) and Lewy neurites (LNs) are key hallmarks. Glia are more than mere bystanders that simply support neurons, they actively contribute to almost every aspect of neuronal development and function; glial dysregulation has been implicated in a series of neurodegenerative diseases including PD. Importantly, amounting evidence has added glial activation and neuroinflammation as new features of PD onset and progression. Thus, gaining a better understanding of glia, especially neuron-glia crosstalk, will not only provide insight into brain physiology events but also advance our knowledge of PD pathologies. This review addresses the current understanding of α-syn pathogenesis in PD, with a focus on neuron-glia crosstalk. Particularly, the transmission of α-syn between neurons and glia, α-syn-induced glial activation, and feedbacks of glial activation on DA neuron degeneration are thoroughly discussed. In addition, α-syn aggregation, iron deposition, and glial activation in regulating DA neuron ferroptosis in PD are covered. Lastly, we summarize the preclinical and clinical therapies, especially targeting glia, in PD treatments. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Therapeutics of Parkinson's Disease 2022)

► Show Figures

Figure 1

28 pages, 1876 KiB

Open AccessReview

Molecular Pathways Involved in LRRK2-Linked Parkinson’s Disease: A Systematic Review

by Ailyn Irvita Ravinther, Hemaniswarri Dewi Dewadas, Shi Ruo Tong, Chai Nien Foo, Yu-En Lin, Cheng-Ting Chien and Yang Mooi Lim

Int. J. Mol. Sci. 2022, 23(19), 11744; https://doi.org/10.3390/ijms231911744 - 3 Oct 2022

Cited by 6 | Viewed by 3484

Abstract

Parkinson’s disease is one of the most common neurodegenerative diseases affecting the ageing population, with a prevalence that has doubled over the last 30 years. As the mechanism of the disease is not fully elucidated, the current treatments are unable to effectively prevent neurodegeneration. Studies have found that mutations in Leucine-rich-repeat-kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). Moreover, aberrant (higher) LRRK2 kinase activity has an influence in idiopathic PD as well. Hence, the aim of this review is to categorize and synthesize current information related to LRRK2-linked PD and present the factors associated with LRRK2 that can be targeted therapeutically. A systematic review was conducted using the databases PubMed, Medline, SCOPUS, SAGE, and Cochrane (January 2016 to July 2021). Search terms included “Parkinson’s disease”, “mechanism”, “LRRK2”, and synonyms in various combinations. The search yielded a total of 988 abstracts for initial review, 80 of which met the inclusion criteria. Here, we emphasize molecular mechanisms revealed in recent in vivo and in vitro studies. By consolidating the recent updates in the field of LRRK2-linked PD, researchers can further evaluate targets for therapeutic application. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Therapeutics of Parkinson's Disease 2022)

► Show Figures