Can We Treat Neurodegenerative Proteinopathies by Enhancing Protein Degradation?
Mov Disord
; 37(7): 1346-1359, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35579450
ABSTRACT
Neurodegenerative proteinopathies are defined as a class of neurodegenerative disorders, with either genetic or sporadic age-related onset, characterized by the pathological accumulation of aggregated protein deposits. These mainly include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) as well as frontotemporal lobar degeneration (FTLD). The deposition of abnormal protein aggregates in the brain of patients affected by these disorders is thought to play a causative role in neuronal loss and disease progression. On that account, the idea of improving the clearance of pathological protein aggregates has taken hold as a potential therapeutic strategy. Among the possible approaches to pursue for reducing disease protein accumulation, there is the stimulation of the main protein degradation machineries of eukaryotic cells the ubiquitin proteasomal system (UPS) and autophagy lysosomal pathway (ALP). Of note, several clinical trials testing the efficacy of either UPS- or ALP-active compounds are currently ongoing. Here, we discuss the main gaps and controversies emerging from experimental studies and clinical trials assessing the therapeutic efficacy of modulators of either the UPS or ALP in neurodegenerative proteinopathies, to gather whether they may constitute a real gateway from these disorders. © 2022 International Parkinson and Movement Disorder Society.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Frontotemporal Lobar Degeneration
/
Amyotrophic Lateral Sclerosis
Limits:
Humans
Language:
En
Journal:
Mov Disord
Journal subject:
NEUROLOGIA
Year:
2022
Type:
Article
Affiliation country:
Israel