A look back at the prodromal findings in Parkinson’s disease DOI Creative Commons
Seyed-Amirabbas Ahadiat, Zeinab Hosseinian

Bulletin of the National Research Centre/Bulletin of the National Research Center, Journal Year: 2023, Volume and Issue: 47(1)

Published: Nov. 20, 2023

Abstract Background Parkinson's disorder is a neurodegenerative illness that displays motor and non-motor manifestations. There no definite cause of disorder, nor there medicine or treatment to prevent it. Main body the abstract Non-motor manifestations are referred be progressive symptoms by medical specialists since they might emerge chronically several years before symptoms. Among these loss smell, constipation, sleep melancholy, sexual dysfunction, depression. In this paper, we focus on different aspects related (PD) prodromal features their prevalence in PD patients, pathophysiology, (if possible), impact diagnosis, prognosis life patients. Short conclusion All people who present with non prodermal should considered for further tests early diagnosis disease.

Language: Английский

The involvement of α-synucleinopathy in the disruption of microglial homeostasis contributes to the pathogenesis of Parkinson’s disease DOI Creative Commons

Yongzhen Miao,

Hongrui Meng

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 12, 2024

The intracellular deposition and intercellular transmission of α-synuclein (α-syn) are shared pathological characteristics among neurodegenerative disorders collectively known as α-synucleinopathies, including Parkinson's disease (PD). Although the precise triggers α-synucleinopathies remain unclear, recent findings indicate that disruption microglial homeostasis contributes to pathogenesis PD. Microglia play a crucial role in maintaining optimal neuronal function by ensuring homeostatic environment, but this is disrupted during progression α-syn pathology. involvement microglia accumulation, uptake, clearance aggregated proteins critical for managing spread caused This review summarizes current knowledge on interrelationships between focusing remarkable ability recognize internalize extracellular through diverse pathways. process intracellularly intercellularly facilitate aggregation cell-to-cell propagation. conformational state distinctly influences inflammation, which can affect peripheral immune cells such macrophages lymphocytes may regulate α-synucleinopathies. We also discuss ongoing research efforts identify potential therapeutic approaches targeting both accumulation inflammation Video Abstract.

Language: Английский

Citations

7
Brain incoming call from glia during neuroinflammation: Roles of extracellular vesicles DOI Creative Commons
Francesco D’Egidio, Vanessa Castelli, Michele d’Angelo

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 201, P. 106663 - 106663

Published: Sept. 7, 2024

Language: Английский

Citations

6
Inhibition of LRRK2 kinase activity rescues deficits in striatal dopamine physiology in VPS35 p.D620N knock-in mice DOI Creative Commons
Mengfei Bu, Jordan Follett, Isaac Deng

et al.

npj Parkinson s Disease, Journal Year: 2023, Volume and Issue: 9(1)

Published: Dec. 18, 2023

Dysregulation of dopamine neurotransmission profoundly affects motor, motivation and learning behaviors, can be observed during the prodromal phase Parkinson's disease (PD). However, mechanism underlying these pathophysiological changes remains to elucidated. Mutations in vacuolar protein sorting 35 (VPS35) leucine-rich repeat kinase 2 (LRRK2) both lead autosomal dominant PD, VPS35 LRRK2 may physically interact govern trafficking synaptic cargos within endo-lysosomal network a kinase-dependent manner. To better understand functional role on physiology, we examined Vps35 haploinsufficient (Haplo) p.D620N knock-in (VKI) mice how their behavior, kinetics biochemistry are influenced by inhibitors. We found significantly elevates LRRK2-mediated phosphorylation Rab10, Rab12 Rab29. In contrast, haploinsufficiency reduces Rab12. While striatal transporter (DAT) expression function is similarly impaired VKI Haplo mice, that physiology normalized treatment with inhibitor, MLi-2. As corollary, animals show significant increase amphetamine induced hyperlocomotion, compared also abolished Taken together, data confers gain-of-function respect activity, functionally regulate DAT transmission.

Language: Английский

Citations

9
Clinical characteristics and pathophysiological properties of newly discovered LRRK2 variants associated with Parkinson's disease DOI Creative Commons
Toshiki Tezuka,

Mayu Ishiguro,

Daisuke Taniguchi

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 199, P. 106571 - 106571

Published: June 18, 2024

Leucine-rich repeat kinase 2 (LRRK2) is the most common gene responsible for familial Parkinson's disease (PD). The product of LRRK2 contains multiple protein domains, including armadillo repeat, ankyrin leucine-rich (LRR), Ras-of-complex (ROC), C-terminal ROC (COR), kinase, and WD40 domains. In this study, we performed genetic screening in our PD cohort, detecting sixteen rare variants. Among them, selected seven variants that are likely to be characterized them terms function, along with clinical information one pathological analysis. were S1120P N1221K LRR domain; I1339M, S1403R, V1447M I1658F D1873H COR domain. activity N1221K, V1447M, toward Rab10, a well-known phosphorylation substrate, was higher than wild-type LRRK2. showed enhanced self-association activity, whereas S1403R reduced microtubule-binding activity. Pathological analysis patient variant also performed, which revealed Lewy pathology brainstem. No functional alterations detected I1339M However, carrying had heterozygous Glucosylceramidase beta 1 (GBA1) L444P variant. conclusion, potentially associated PD. Five different domains exhibited altered properties self-association, suggesting each domain may contribute progression ways.

Language: Английский

Citations

2
Evaluation of Neuroinflammatory Contribution to Neurodegeneration in LRRK2 Drosophila Models DOI Creative Commons
Nam Hoai Nguyen, Grazia Galleri,

A.L. Rassu

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1555 - 1555

Published: July 12, 2024

Pathological mutations in the LRRK2 gene are major genetic cause of Parkinson’s disease (PD). Although several animal models with either down- or over-expression have been developed, physiological function remains elusive. is constitutively expressed various tissues including neurons and glial cells, but importantly, it at low levels dopaminergic neurons, further contributing to cryptic LRRK2. Significant protein mRNA detected peripheral blood mononuclear lymph nodes, spleen, primary microglia, strongly suggesting contribution inflammatory cells neuronal degeneration. In this research article, using Drosophila models, we were able demonstrate a significant pathological phenotype. Furthermore, Drosophila, neurodegeneration associated important increase specific peptides. Finally, levetiracetam, compound widely used human therapy treat epilepsy, was rescue both degeneration neuroinflammation.

Language: Английский

Citations

2
Influence of aging, mitochondrial dysfunction, and inflammation on Parkinson’s disease DOI Creative Commons
Davide Cossu, Nobutaka Hattori

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(6), P. 1197 - 1198

Published: Sept. 22, 2023

Department of Neurology, Juntendo University, Tokyo, Japan (Cossu D, Hattori N) Biomedical Sciences, Sassari Sassari, Italy D) *Correspondence to: Davide Cossu, PhD, [email protected]. This is an open-access article distributed under the terms Creative Commons Attribution-Noncommercial-Share Alike 4.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided original work properly cited.

Language: Английский

Citations

6
Infectious Microorganisms Seen as Etiologic Agents in Parkinson’s Disease DOI Creative Commons
Alina Zorina Stroe,

Sanda Jurja,

Mihaela Cezarina Mehedinţi

et al.

Life, Journal Year: 2023, Volume and Issue: 13(3), P. 805 - 805

Published: March 16, 2023

Infections represent a possible risk factor for parkinsonism and Parkinson’s disease (PD) based on information from epidemiology fundamental science. The is unclear the majority of agents. Moreover, latency between infection PD seems to be very varied often lengthy. In this review, evidence supporting potential involvement infectious microorganisms in development examined. Consequently, it crucial determine cause give additional treatment accordingly. Infection an intriguing suggestion regarding disease. These findings demonstrate that persistent with viral bacterial might As initiating factor, may generate spectrum gut microbiota dysbiosis, engagement glial tissues, neuroinflammation, alpha-synuclein accumulation, all which trigger worsen onset also contribute its progression. Still uncertain primary etiology infection. pathophysiology remains matter debate. Furthermore, study required if patients develop due or solely since they are more sensitive causes.

Language: Английский

Citations

4
LRRK2; Communicative Role in the Treatment of Parkinson’s Disease and Ulcerative Colitis Overlapping DOI
Naser‐Aldin Lashgari, Nazanin Momeni Roudsari, Amirhossein Niknejad

et al.

CNS & Neurological Disorders - Drug Targets, Journal Year: 2024, Volume and Issue: 23(10), P. 1177 - 1188

Published: Jan. 26, 2024

Background: Involvement of gastrointestinal inflammation in Parkinson’s disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved the etiology both PD inflammatory bowel (IBD). Transformations leucine-rich recurrent kinase 2 (LRRK2) are among best hereditary supporters IBD PD. Elevated levels LRRK2 been reported stimulated colonic tissue from patients peripheral invulnerable cells irregular patients; thus, it thought that directs cycles. Objective: Since its revelation, has seriously linked neurons, albeit various lines proof affirmed profoundly communicated cells. Subsequently, might sit at a junction by which stomach higher be biomarker expanded risk for inconsistent or potentially may address manageable helpful objective incendiary sicknesses increment Here, we discuss how share covering aggregates, especially regarding present inhibitors, could ongoing treatments. Method: English data were obtained Google Scholar, PubMed, Scopus, Cochrane library studies published between 1990-December 2022. Result: Inhibitors pathway can considered as novel treatment approaches treatment. Conclusion: Common mediators pathways pathophysiology PD, majorly correlated with situations. Such diseases used further clinical investigations.

Language: Английский

Citations

1
Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology DOI
Fatema Currim,

Reeya Tanwar,

Josephine M. Brown-Leung

et al.

NeuroToxicology, Journal Year: 2024, Volume and Issue: 103, P. 266 - 287

Published: July 1, 2024

Language: Английский

Citations

1
A look back at the prodromal findings in Parkinson’s disease DOI Creative Commons
Seyed-Amirabbas Ahadiat, Zeinab Hosseinian

Bulletin of the National Research Centre/Bulletin of the National Research Center, Journal Year: 2023, Volume and Issue: 47(1)

Published: Nov. 20, 2023

Abstract Background Parkinson's disorder is a neurodegenerative illness that displays motor and non-motor manifestations. There no definite cause of disorder, nor there medicine or treatment to prevent it. Main body the abstract Non-motor manifestations are referred be progressive symptoms by medical specialists since they might emerge chronically several years before symptoms. Among these loss smell, constipation, sleep melancholy, sexual dysfunction, depression. In this paper, we focus on different aspects related (PD) prodromal features their prevalence in PD patients, pathophysiology, (if possible), impact diagnosis, prognosis life patients. Short conclusion All people who present with non prodermal should considered for further tests early diagnosis disease.

Language: Английский

Citations

1