Progressive decline of glucocerebrosidase in aging and P arkinson's disease

EM Rocha, GA Smith, E Park, H Cao… - Annals of clinical …, 2015 - Wiley Online Library
EM Rocha, GA Smith, E Park, H Cao, E Brown, P Hallett, O Isacson
Annals of clinical and translational neurology, 2015Wiley Online Library
The principal risk factor for developing most adult onset neurodegenerative diseases is
aging, with incidence rising significantly after age 50. Despite research efforts, the causes of
P arkinson's disease (PD) remain unknown. As neurons age, they show signs of diminished
lysosomal and mitochondrial function, including increased oxidative stress and
accumulation of misfolded proteins, and these changes become exacerbated PD. We show
that activity of the lysosomal hydrolase glucocerebrosidase gradually diminishes with age in …
Abstract
The principal risk factor for developing most adult onset neurodegenerative diseases is aging, with incidence rising significantly after age 50. Despite research efforts, the causes of Parkinson's disease (PD) remain unknown. As neurons age, they show signs of diminished lysosomal and mitochondrial function, including increased oxidative stress and accumulation of misfolded proteins, and these changes become exacerbated PD. We show that activity of the lysosomal hydrolase glucocerebrosidase gradually diminishes with age in the substantia nigra and putamen of healthy controls. This reduction is comparable to glucocerebrosidase activity in GBA1‐mutation carrier PD patients. These data, demonstrate for the first time that an age‐dependent reduction in glucocerebrosidase activity may lower the threshold for developing PD.
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