From Synaptic Dysfunction to Neuroprotective Strategies in Genetic Parkinson's Disease: Lessons From LRRK2.
LRRK2
Parkinson’s disease
mitochondrial dysfunction
neuroprotection
synaptic dysfunction
α-synuclein
Journal
Frontiers in cellular neuroscience
ISSN: 1662-5102
Titre abrégé: Front Cell Neurosci
Pays: Switzerland
ID NLM: 101477935
Informations de publication
Date de publication:
2020
2020
Historique:
received:
08
01
2020
accepted:
12
05
2020
entrez:
28
8
2020
pubmed:
28
8
2020
medline:
28
8
2020
Statut:
epublish
Résumé
The pathogenesis of Parkinson's disease (PD) is thought to rely on a complex interaction between the patient's genetic background and a variety of largely unknown environmental factors. In this scenario, the investigation of the genetic bases underlying familial PD could unveil key molecular pathways to be targeted by new disease-modifying therapies, still currently unavailable. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are responsible for the majority of inherited familial PD cases and can also be found in sporadic PD, but the pathophysiological functions of LRRK2 have not yet been fully elucidated. Here, we will review the evidence obtained in transgenic LRRK2 experimental models, characterized by altered striatal synaptic transmission, mitochondrial dysfunction, and α-synuclein aggregation. Interestingly, the processes triggered by mutant LRRK2 might represent early pathological phenomena in the pathogenesis of PD, anticipating the typical neurodegenerative features characterizing the late phases of the disease. A comprehensive view of LRRK2 neuronal pathophysiology will support the possible clinical application of pharmacological compounds targeting this protein, with potential therapeutic implications for patients suffering from both familial and sporadic PD.
Identifiants
pubmed: 32848606
doi: 10.3389/fncel.2020.00158
pmc: PMC7399363
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
158Subventions
Organisme : Medical Research Council
ID : MR/N029453/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P007058/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/1
Pays : United Kingdom
Organisme : Parkinson's UK
ID : J-0901
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_EX_MR/N50192X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M024962/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Mancini, Mazzocchetti, Sciaccaluga, Megaro, Bellingacci, Beccano-Kelly, Di Filippo, Tozzi and Calabresi.
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