Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Recent Molecular Research of Parkinson's Disease
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Recent Molecular Research of Parkinson's Disease

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: 25 May 2024 | Viewed by 5713

Special Issue Editors

Dr. Toshiharu Nagatsu

E-Mail Website
Guest Editor
School of Medicine, Fujita Health University, Aichi, Toyoake 470-1192, Japan
Interests: clinical neuroscience; neuropsychiatry
Dr. Hirohisa Watanabe

E-Mail Website
Guest Editor
Department of Neurology, Fujita Health University, Aichi, Toyoake 470-1192, Japan
Interests: Parkinson's disease; aging; brain network; neuroradiology; brain energy; biomarker

Special Issue Information

Dear Colleagues, 

Since James Parkinson first described the movement disorder now termed Parkinson’s disease (PD) in 1887, research on in the 20th century has contributed to the elucidation of PD pathophysiology, such as discovery of the two main histopathological hallmarks, Lewy bodies and neuromelanin, in the brain, deficiency of dopamine in the striatum due to death of nigrostriatal dopamine neurons in the substantia nigra, and to the development of symptomatic pharmacotherapies, particularly levodopa. In the 21st century, further progress in elucidating the molecular mechanism has been made in new research developments. Various causative genes (e.g., PARKs) have been discovered in the small cohort with familial PD (fPD, ~5%). Alpha-synuclein, a main protein in Lewy bodies, was found not only in the brain in “brain-first PD” but also in the whole body and in the intestine, where it is produced by intestinal microbiota in “body-first PD”. Most cases, which are of sporadic PD (sPD, ~95%) without family history, are aging-related, and the molecular mechanism has been intensively explored. Oxidative stress by internal (genetic) and external factors might trigger endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which results in production of reactive oxygen species (ROS), with subsequent impairment of intracellular proteolysis due to dysfunctions in the autophagy (mitophagy) and ubiquitin–proteasomal systems, alpha-synuclein oligomer accumulation and neuromelanin accumulation with iron, neuroinflammation, and finally neuronal death. The finding of early markers of PD and early diagnosis by neuroimaging before the onset of movement disorders has been extensively studied. Regarding treatment, the development of new therapies is in progress, with drug development to halt progression and even reverse symptoms, deep-brain stimulation, transcranial magnetic stimulation, cell therapy based on iPS cell-derived dopamine neurons and gene therapy, physical rehabilitation therapy, and psychotherapy such as cognitive behavioral therapy for mental symptoms such as depression. This Special Issue “Recent Molecular Research of Parkinson’s Disease” aims to provide an update on the recent research progress in the mechanism and treatment of PD.

Dr. Toshiharu Nagatsu
Dr. Hirohisa Watanabe
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

  • aging
  • alpha-synuclein
  • autophagy
  • body-first Parkinson’s disease
  • brain-first Parkinson’s disease
  • clinical neuroscience
  • familial Parkinson’s disease (fPD)
  • iron
  • intestinal microbe
  • intracellular proteolysis
  • Lewy bodies
  • mitochondrial dysfunction
  • neuromelanin
  • neuropsychiatry
  • oxidative stress

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Review

28 pages, 1967 KiB  
Review
Parkinson’s Disease: Cells Succumbing to Lifelong Dopamine-Related Oxidative Stress and Other Bioenergetic Challenges
by Hirohisa Watanabe, Johannes M. Dijkstra and Toshiharu Nagatsu
Int. J. Mol. Sci. 2024, 25(4), 2009; https://doi.org/10.3390/ijms25042009 - 07 Feb 2024
Viewed by 944
Abstract
The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). The reasons why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans are [...] Read more.
The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). The reasons why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans are still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite the fact that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support. Full article
(This article belongs to the Special Issue Recent Molecular Research of Parkinson's Disease)
►▼ Show Figures

Figure 1

18 pages, 2581 KiB  
Review
Pathogenic Impact of Fatty Acid-Binding Proteins in Parkinson’s Disease—Potential Biomarkers and Therapeutic Targets
by Ichiro Kawahata and Kohji Fukunaga
Int. J. Mol. Sci. 2023, 24(23), 17037; https://doi.org/10.3390/ijms242317037 - 01 Dec 2023
Viewed by 1356
Abstract
Parkinson’s disease is a neurodegenerative condition characterized by motor dysfunction resulting from the degeneration of dopamine-producing neurons in the midbrain. This dopamine deficiency gives rise to a spectrum of movement-related symptoms, including tremors, rigidity, and bradykinesia. While the precise etiology of Parkinson’s disease [...] Read more.
Parkinson’s disease is a neurodegenerative condition characterized by motor dysfunction resulting from the degeneration of dopamine-producing neurons in the midbrain. This dopamine deficiency gives rise to a spectrum of movement-related symptoms, including tremors, rigidity, and bradykinesia. While the precise etiology of Parkinson’s disease remains elusive, genetic mutations, protein aggregation, inflammatory processes, and oxidative stress are believed to contribute to its development. In this context, fatty acid-binding proteins (FABPs) in the central nervous system, FABP3, FABP5, and FABP7, impact α-synuclein aggregation, neurotoxicity, and neuroinflammation. These FABPs accumulate in mitochondria during neurodegeneration, disrupting their membrane potential and homeostasis. In particular, FABP3, abundant in nigrostriatal dopaminergic neurons, is responsible for α-synuclein propagation into neurons and intracellular accumulation, affecting the loss of mesencephalic tyrosine hydroxylase protein, a rate-limiting enzyme of dopamine biosynthesis. This review summarizes the characteristics of FABP family proteins and delves into the pathogenic significance of FABPs in the pathogenesis of Parkinson’s disease. Furthermore, it examines potential novel therapeutic targets and early diagnostic biomarkers for Parkinson’s disease and related neurodegenerative disorders. Full article
(This article belongs to the Special Issue Recent Molecular Research of Parkinson's Disease)
►▼ Show Figures

Figure 1

18 pages, 3984 KiB  
Review
Involvement of Mitochondria in Parkinson’s Disease
by Chi-Jing Choong and Hideki Mochizuki
Int. J. Mol. Sci. 2023, 24(23), 17027; https://doi.org/10.3390/ijms242317027 - 01 Dec 2023
Cited by 4 | Viewed by 1532
Abstract
Mitochondrial dysregulation, such as mitochondrial complex I deficiency, increased oxidative stress, perturbation of mitochondrial dynamics and mitophagy, has long been implicated in the pathogenesis of PD. Initiating from the observation that mitochondrial toxins cause PD-like symptoms and mitochondrial DNA mutations are associated with [...] Read more.
Mitochondrial dysregulation, such as mitochondrial complex I deficiency, increased oxidative stress, perturbation of mitochondrial dynamics and mitophagy, has long been implicated in the pathogenesis of PD. Initiating from the observation that mitochondrial toxins cause PD-like symptoms and mitochondrial DNA mutations are associated with increased risk of PD, many mutated genes linked to familial forms of PD, including PRKN, PINK1, DJ-1 and SNCA, have also been found to affect the mitochondrial features. Recent research has uncovered a much more complex involvement of mitochondria in PD. Disruption of mitochondrial quality control coupled with abnormal secretion of mitochondrial contents to dispose damaged organelles may play a role in the pathogenesis of PD. Furthermore, due to its bacterial ancestry, circulating mitochondrial DNAs can function as damage-associated molecular patterns eliciting inflammatory response. In this review, we summarize and discuss the connection between mitochondrial dysfunction and PD, highlighting the molecular triggers of the disease process, the intra- and extracellular roles of mitochondria in PD as well as the therapeutic potential of mitochondrial transplantation. Full article
(This article belongs to the Special Issue Recent Molecular Research of Parkinson's Disease)
►▼ Show Figures

Figure 1

18 pages, 2106 KiB  
Review
The Role of Immune Dysfunction in Parkinson’s Disease Development
by Davide Cossu, Taku Hatano and Nobutaka Hattori
Int. J. Mol. Sci. 2023, 24(23), 16766; https://doi.org/10.3390/ijms242316766 - 26 Nov 2023
Cited by 2 | Viewed by 1428
Abstract
Recent research has unveiled intriguing insights suggesting that the body’s immune system may be implicated in Parkinson’s disease (PD) development. Studies have observed disparities in pro-inflammatory and anti-inflammatory markers between PD patients and healthy individuals. This finding underscores the potential influence of immune [...] Read more.
Recent research has unveiled intriguing insights suggesting that the body’s immune system may be implicated in Parkinson’s disease (PD) development. Studies have observed disparities in pro-inflammatory and anti-inflammatory markers between PD patients and healthy individuals. This finding underscores the potential influence of immune system dysfunction in the genesis of this condition. A dysfunctional immune system can serve as a primary catalyst for systemic inflammation in the body, which may contribute to the emergence of various brain disorders. The identification of several genes associated with PD, as well as their connection to neuroinflammation, raises the likelihood of disease susceptibility. Moreover, advancing age and mitochondrial dysfunction can weaken the immune system, potentially implicating them in the onset of the disease, particularly among older individuals. Compromised integrity of the blood–brain barrier could facilitate the immune system’s access to brain tissue. This exposure may lead to encounters with native antigens or infections, potentially triggering an autoimmune response. Furthermore, there is mounting evidence supporting the notion that gut dysbiosis might represent an initial trigger for brain inflammation, ultimately promoting neurodegeneration. In this comprehensive review, we will delve into the numerous hypotheses surrounding the role of both innate and adaptive immunity in PD. Full article
(This article belongs to the Special Issue Recent Molecular Research of Parkinson's Disease)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop