2016
DOI: 10.1002/mds.26562
|View full text |Cite
|
Sign up to set email alerts
|

Lysosomal Dysfunction and α‐Synuclein Aggregation in Parkinson's Disease: Diagnostic Links

Abstract: Lysosomal impairment is increasingly recognized as a central event in the pathophysiology of PD. Genetic associations between lysosomal storage disorders, including Gaucher disease and PD, highlight common risk factors and pathological mechanisms. Because the autophagy-lysosomal system is involved in the intralysosomal hydrolysis of dysfunctional proteins, lysosomal impairment may contribute to α-synuclein aggregation in PD. The degradation of α-synuclein is a complex process involving different proteolytic me… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

5
101
0

Year Published

2016
2016
2024
2024

Publication Types

Select...
9

Relationship

1
8

Authors

Journals

citations
Cited by 141 publications
(106 citation statements)
references
References 132 publications
(329 reference statements)
5
101
0
Order By: Relevance
“…General lysosomal dysfunction as well as alterations in CatD levels and activity are implicated in the pathogenesis of PD (Qiao et al, 2008; Sevlever et al, 2008; Manzoni and Lewis, 2013; Matrone et al, 2016; Moors et al, 2016). To further analyze the impact of αSyn on lysosomal integrity in general and on CatD function in particular, we used a yeast model for PD based on the heterologous expression of human αSyn.…”
Section: Resultsmentioning
confidence: 99%
“…General lysosomal dysfunction as well as alterations in CatD levels and activity are implicated in the pathogenesis of PD (Qiao et al, 2008; Sevlever et al, 2008; Manzoni and Lewis, 2013; Matrone et al, 2016; Moors et al, 2016). To further analyze the impact of αSyn on lysosomal integrity in general and on CatD function in particular, we used a yeast model for PD based on the heterologous expression of human αSyn.…”
Section: Resultsmentioning
confidence: 99%
“…Higher order oligomeric α-syn species are degraded by macroautophagy while monomeric and dimeric species are degraded by chaperone mediated autophagy or by the ubiquitin proteasome system 35 . However, it has been established that aggregation prone mutants of α-syn, over-expression of α-syn and LB-like α-syn inclusions inhibit autophagy, resulting in a vicious cycle where α-syn degradation is impaired, leading to larger aggregates and eventually cell death 36 . Furthermore, in order to maintain cellular homeostasis, the inhibition of autophagy also leads to an increase in exocytosis 3739 .…”
Section: Discussionmentioning
confidence: 99%
“…In support of this theory, the last decade has witnessed an increasing amount of genetic evidence implicating the lysosomal system as a central mechanism in the pathobiology of PD (Kalia and Lang 2015; Moors et al 2016; Vekrellis et al 2011; Wong and Krainc 2016). As previously described, heterogeneous mutations in GBA confer high risk for PD, and pathogenic variants in ATP13A2 , encoding a lysosomal ATPase, are responsible for a very rare cause of parkinsonism (Park et al 2015).…”
Section: A Glimpse Into Much Larger Networkmentioning
confidence: 99%