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Evaluation of Strategies for Measuring Lysosomal Glucocerebrosidase Activity
Author(s) -
Ysselstein Daniel,
Young Tiffany J.,
Nguyen Maria,
Padmanabhan Shalini,
Hirst Warren D.,
Dzamko Nicolas,
Krainc Dimitri
Publication year - 2021
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28815
Subject(s) - glucocerebrosidase , dementia , parkinson's disease , dementia with lewy bodies , disease , lewy body , neuroscience , movement disorders , psychology , medicine , bioinformatics , pathology , biology
ABSTRACT Mutations in GBA1 , which encode for the protein glucocerebrosidase (GCase), are the most common genetic risk factor for Parkinson's disease and dementia with Lewy bodies. In addition, growing evidence now suggests that the loss of GCase activity is also involved in onset of all forms of Parkinson's disease, dementia with Lewy bodies, and other dementias, such as progranulin‐linked frontal temporal dementia. As a result, there is significant interest in developing GCase‐targeted therapies that have the potential to stop or slow progression of these diseases. Despite this interest in GCase as a therapeutic target, there is significant inconsistency in the methodology for measuring GCase enzymatic activity in disease‐modeling systems and patient populations, which could hinder progress in developing GCase therapies. In this review, we discuss the different strategies that have been developed to assess GCase activity and highlight the specific strengths and weaknesses of these approaches as well as the gaps that remain. We also discuss the current and potential role of these different methodologies in preclinical and clinical development of GCase‐targeted therapies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society