Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology DOI Creative Commons
Hirohisa Watanabe, Sayuri Shima, Kazuya Kawabata

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 22, 2025

Parkinson’s disease (PD) involves the disruption of brain energy homeostasis. This encompasses broad-impact factors such as mitochondrial dysfunction, impaired glycolysis, and other metabolic disturbances, like disruptions in pentose phosphate pathway purine metabolism. Cortical hubs, which are highly connected regions essential for coordinating multiple functions, require significant due to their dense synaptic activity long-range connections. Deficits ATP production PD can severely impair these hubs. The imbalance also affects subcortical regions, including massive axonal arbors striatum substantia nigra pars compacta neurons, high demand. decline may result α -synuclein accumulation, autophagy-lysosomal system impairment, neuronal network breakdown accelerated neurodegeneration. We propose an “ATP Supply–Demand Mismatch Model” help explain pathogenesis PD. model emphasizes how deficits drive pathological protein aggregation, autophagy, degeneration key networks, contributing both motor non-motor symptoms.

Language: Английский

Teaghrelin protected dopaminergic neurons in MPTP‐induced Parkinson's disease animal model by promoting PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC1‐α‐mediated mitochondrial biogenesis DOI
Cian‐Fen Jhuo, Chun‐Jung Chen, Jason T. C. Tzen

et al.

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(7), P. 4022 - 4034

Published: April 15, 2024

Abstract Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play significant role pathologic development progression the disease. Teaghrelin, unique bioactive compound some oolong tea varieties, has been demonstrated protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding ghrelin receptor activate AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), byproduct prohibited drug, evaluate oral efficacy teaghrelin on PD monitoring motor dysfunction mice open field, pole, bean walking tests. The results showed that MPTP‐induced significantly attenuated supplementation. Tyrosine hydroxylase dopamine transporter protein were found reduced striatum midbrain MPTP‐treated mice, mitigated Furthermore, administration enhanced mitophagy mitochondria biogenesis, which maintained cell homeostasis prevented accumulation αSyn apoptosis‐related proteins. It seemed protected dopaminergic neurons increasing PINK1/Parkin‐mediated AMPK/SIRT1/PGC‐1α‐mediated highlighting its potential therapeutic maintaining function PD.

Language: Английский

Citations

11
The central role of the NLRP3 inflammasome pathway in the pathogenesis of age-related diseases in the eye and the brain DOI
Jack Jonathan Maran,

Moradeke M. Adesina,

Colin Green

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 88, P. 101954 - 101954

Published: May 15, 2023

Language: Английский

Citations

18
Role of F-actin-mediated endocytosis and exercise in mitochondrial transplantation in an experimental Parkinson's disease mouse model DOI Open Access
Rachit Jain,

Nusrat Begum,

Shruti Rajan

et al.

Mitochondrion, Journal Year: 2023, Volume and Issue: 74, P. 101824 - 101824

Published: Nov. 29, 2023

Language: Английский

Citations

16
Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson’s Disease DOI Creative Commons
Yashumati Ratan, Aishwarya Rajput, Ashutosh Pareek

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(1), P. 73 - 73

Published: Jan. 5, 2024

Parkinson’s disease (PD) is the second most prevalent neurodegenerative movement disorder worldwide, which primarily characterized by motor impairments. Even though multiple hypotheses have been proposed over decades that explain pathogenesis of PD, presently, there are no cures or promising preventive therapies for PD. This could be attributed to intricate pathophysiology PD and poorly understood molecular mechanism. To address these challenges comprehensively, a thorough model imperative nuanced understanding PD’s underlying pathogenic mechanisms. review offers detailed analysis current state knowledge regarding mechanisms with particular emphasis on roles played gene-based factors in disease’s development progression. study includes an extensive discussion proteins mutations primary genes linked including α-synuclein, GBA1, LRRK2, VPS35, PINK1, DJ-1, Parkin. Further, this explores plausible DAergic neural loss, non-motor non-dopaminergic pathologies, risk associated The present will encourage related research fields understand better analyze status biochemical might contribute design efficacious safe treatment strategies future endeavors.

Language: Английский

Citations

7
A naturally occurring variant of SHLP2 is a protective factor in Parkinson’s disease DOI Creative Commons
Su‐Jeong Kim, Brendan Miller, Nicolas Hartel

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(2), P. 505 - 517

Published: Jan. 3, 2024

Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate functional role PD-associated mtSNP that impacts mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.2158 T > C, PD risk, within small open reading frame encoding SHLP2. This results in an alternative form SHLP2 (lysine 4 replaced arginine; K4R). Using targeted mass spectrometry, detect specific tryptic fragments neuronal cells and demonstrate its binding to mitochondrial complex 1. Notably, observe K4R variant, exhibits increased stability compared WT Additionally, both show enhanced protection against dysfunction vitro experiments confer PD-inducing toxin, 1 inhibitor, mouse model. study sheds light on consequences C provides insights into potential by which may reduce PD.

Language: Английский

Citations

6
Therapeutic approaches targeting aging and cellular senescence in Huntington's disease DOI Creative Commons
Asif Ahmad Bhat, Ehssan Moglad, Muhammad Afzal

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(10)

Published: Oct. 1, 2024

Huntington's disease (HD) is a devastating neurodegenerative that manifested by gradual loss of physical, cognitive, and mental abilities. As the advances, age has major impact on pathogenic signature mutant huntingtin (mHTT) protein aggregation. This review aims to explore intricate relationship between aging, mHTT toxicity, cellular senescence in HD. Scientific data interplay mHTT, HD were collected from several academic databases, including PubMed, Google Scholar, Google, ScienceDirect. The search terms employed "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," "CELLULAR SENESCENCE." Additionally, gather information molecular mechanisms potential therapeutic targets, was extended include relevant such as "DNA DAMAGE," "OXIDATIVE STRESS," "AUTOPHAGY." According research, aging leads worsening pathophysiology through some processes. result accumulation, promoted, which causes DNA damage, oxidative stress, decreased autophagy, increased inflammatory responses. Pro-inflammatory cytokines other substances are released senescent cells, may worsen neuronal damage course disease. It been shown treatments directed at these pathways reduce symptoms enhance longevity experimental animals, pointing new possibility treating condition. Through their amplification harmful effects play crucial roles development Comprehending interplays creates novel opportunities for measures targeted alleviating enhancing patients' quality life.

Language: Английский

Citations

6
Formoterol attenuated mitochondrial dysfunction in rotenone-induced Parkinson's disease in a rat model: Role of PINK-1/PARKIN and PI3K/Akt/CREB/BDNF/TrKB axis DOI

Haneen Y. Khidr,

Noha F. Hassan,

Sahar S. Abdelrahman

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 125, P. 111207 - 111207

Published: Nov. 11, 2023

Language: Английский

Citations

15
Mitochondrial dysfunction-targeting therapeutics of natural products in Parkinson’s disease DOI Creative Commons

Ting He,

Xiaoyan Lin, Anping Su

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: May 10, 2023

Parkinson’s disease (PD), the second most common neurodegenerative worldwide, often occurs in middle-aged and elderly individuals. The pathogenesis of PD is complex includes mitochondrial dysfunction, oxidative stress. Recently, natural products with multiple structures their bioactive components have become one important resources for small molecule drug research targeting dysfunction. Multiple lines studies proven that display ameliorative benefits treatment by regulating Therefore, a comprehensive search recent published articles between 2012 2022 PubMed, Web Science, Elesvier, Wliey Springer was carried out, focusing on original publications related to against restoring This paper presented mechanisms various kinds PD-related dysfunction regulation provided evidence are promising be developed as drugs therapeutics.

Language: Английский

Citations

13
Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach DOI
Sara Martínez, Oihane E. Albóniga, María Rosa López‐Huertas

et al.

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(8), P. 3025 - 3040

Published: April 3, 2024

Despite the recent and increasing knowledge surrounding COVID-19 infection, underlying mechanisms of persistence symptoms for a long time after acute infection are still not completely understood. Here, multiplatform mass spectrometry-based approach was used metabolomic lipidomic profiling human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered mild 40). Untargeted analysis using CE-ESI(+/−)-TOF-MS GC-Q-MS performed. Additionally, LC-ESI(+/−)-QTOF-MS based on an in-house library revealed 447 lipid species identified high confidence annotation level. The integration complementary analytical platforms has allowed comprehensive metabolic characterization alterations in disease that found 46 relevant metabolites which discriminate between patients. We report specific altered COVID, mainly related decrease amino acid metabolism ceramide levels increase tricarboxylic (TCA) cycle, reinforcing evidence impaired function. most shown this study will help better understand insights syndrome by providing deeper basis pathology.

Language: Английский

Citations

5
Spatially resolved multiomics on the neuronal effects induced by spaceflight in mice DOI Creative Commons
Yuvarani Masarapu, Egle Cekanaviciute, Žaneta Andrusivová

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 11, 2024

Abstract Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate impact spaceflight on mouse brain in female mice. Our comparative analysis between ground control spaceflight-exposed animals revealed alterations essential processes including neurogenesis, synaptogenesis synaptic transmission, particularly affecting cortex, hippocampus, striatum neuroendocrine structures. Additionally, observed astrocyte activation signs immune dysfunction. At pathway level, some spaceflight-induced changes exhibit similarities neurodegenerative disorders, marked oxidative stress protein misfolding. integrated serves as stepping stone towards understanding CNS impairments at level individual regions cell types, provides basis comparison future studies. For broader scientific impact, all datasets from study are available through interactive data portal, well National Aeronautics Space Administration (NASA) Open Science Data Repository (OSDR).

Language: Английский

Citations

5