Genetics and pathogenesis of Parkinson's syndrome

H Ye, LA Robak, M Yu, M Cykowski… - Annual Review of …, 2023 - annualreviews.org
Parkinson's disease (PD) is clinically, pathologically, and genetically heterogeneous,
resisting distillation to a single, cohesive disorder. Instead, each affected individual develops …

The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

T Yadati, T Houben, A Bitorina, R Shiri-Sverdlov - Cells, 2020 - mdpi.com
Cathepsins are the most abundant lysosomal proteases that are mainly found in acidic
endo/lysosomal compartments where they play a vital role in intracellular protein …

Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes

M Hu, P Li, C Wang, X Feng, Q Geng, W Chen… - Cell, 2022 - cell.com
Lysosomes require an acidic lumen between pH 4.5 and 5.0 for effective digestion of
macromolecules. This pH optimum is maintained by proton influx produced by the V-ATPase …

A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci

D Chang, MA Nalls, IB Hallgrímsdóttir, J Hunkapiller… - Nature …, 2017 - nature.com
Common variant genome-wide association studies (GWASs) have, to date, identified> 24
risk loci for Parkinson's disease (PD). To discover additional loci, we carried out a GWAS …

Autophagy in Parkinson's disease

X Hou, JO Watzlawik, FC Fiesel, W Springer - Journal of molecular biology, 2020 - Elsevier
Impaired protein homeostasis and accumulation of damaged or abnormally modified protein
are common disease mechanisms in many neurodegenerative disorders, including …

α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies

YC Wong, D Krainc - Nature medicine, 2017 - nature.com
Alterations in α-synuclein dosage lead to familial Parkinson's disease (PD), and its
accumulation results in synucleinopathies that include PD, dementia with Lewy bodies …

Conformational strains of pathogenic amyloid proteins in neurodegenerative diseases

D Li, C Liu - Nature Reviews Neuroscience, 2022 - nature.com
Amyloid proteins, which are considered 'villains' in many neurodegenerative diseases, form
enigmatic pathological strains that underlie disease pathogenesis and progression. Recent …

Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease

LA Robak, IE Jansen, J Van Rooij, AG Uitterlinden… - Brain, 2017 - academic.oup.com
Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also
potent risk factors for Parkinson's disease. We examined whether a genetic burden of …

Genome-scale metabolic network reconstruction of model animals as a platform for translational research

H Wang, JL Robinson, P Kocabas… - Proceedings of the …, 2021 - National Acad Sciences
Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms
underlying human diseases and metabolic malfunctions. However, the lack of …

α-Synuclein–induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models

JR Mazzulli, F Zunke, O Isacson… - Proceedings of the …, 2016 - National Acad Sciences
Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the
accumulation of protein aggregates comprised of α-synuclein (α-syn). A major barrier in …