Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies
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alpha-Synuclein aggregation and accumulation in Lewy bodies are implicated in progressive loss of dopaminergic neurons in Parkinson disease and related disorders. In neurons, the Hsp70s and their Hsp40-like J-domain co-chaperones are the only known compone ...
In vitro studies of Alzheimer’s disease are based on homogenously seeded neural cells. These studies reveal molecular pathway mechanism related to neurite degeneration, but they cannot analyze interactions between diseased and healthy cells. Furthermore, t ...
Phosphorylation of alpha-synuclein (alpha-syn) at Ser-129 is a hallmark of Parkinson disease and related synucleinopathies. However, the identity of the natural kinases and phosphatases responsible for regulating alpha-syn phosphorylation remain unknown. H ...
American Society for Biochemistry and Molecular Biology2010
α-Synuclein aggregates in Lewy bodies and plays a central role in the pathogenesis of a group of neurodegenerative disorders, known as "Synucleinopathies", including Parkinson's disease. Parkin mutations result in loss of parkin E3-ubiquitin ligase activit ...
A better understanding of the molecular and cellular determinants that influence the pathology of Parkinson's disease (PD) is essential for developing effective diagnostic, preventative and therapeutic strategies to treat this devastating disease. A number ...
Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common causes of both familial and sporadic forms of Parkinson disease and are also associated with diverse pathological alterations. The mechanisms whereby LRRK2 mutations ca ...
In synucleinopathies, including Parkinson's disease, partially ubiquitylated alpha-synuclein species phosphorylated on serine 129 (P(S129)-alpha-synuclein) accumulate abnormally. Parkin, an ubiquitin-protein ligase that is dysfunctional in autosomal recess ...
We explored the relationship between ubiquitin proteasome system (UPS) and lysosomal markers and the formation of alpha-synuclein (alpha-syn) inclusions in nigral neurons in Parkinson disease (PD). Lysosome Associated Membrane Protein 1(LAMP1), Cathepsin D ...
Hyperphosphorylated tau makes up the filamentous intracellular inclusions of several neurodegenerative diseases, including Alzheimer's disease(1). In the disease process, neuronal tau inclusions first appear in the transentorhinal cortex from where they se ...
Background: Missense mutations and multiplications of the alpha-synuclein gene cause autosomal dominant familial Parkinson's disease (PD). alpha-Synuclein protein is also a major component of Lewy bodies, the hallmark pathological inclusions of PD. Therefo ...
