GBA-Associated Parkinson’s Disease and Other Synucleinopathies
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Purpose of Review
GBA mutations are the most common known genetic cause of Parkinson’s disease (PD). Its biological pathway may be important in idiopathic PD, since activity of the enzyme encoded by GBA, glucocerebrosidase, is reduced even among PD patients without GBA mutations. This article describes the structure and function of GBA, reviews recent literature on the clinical phenotype of GBA PD, and suggests future directions for research, counseling, and treatment.
Several longitudinal studies have shown that GBA PD has faster motor and cognitive progression than idiopathic PD and that this effect is dose dependent. New evidence suggests that GBA mutations may be important in multiple system atrophy. Further, new interventional studies focusing on GBA PD are described. These studies may increase the interest of PD patients and caregivers in genetic counseling.
GBA mutation status may help clinicians estimate PD progression, though mechanisms underlying GBA and synucleinopathy require further understanding.
KeywordsParkinson’s disease Glucocerebrosidase Genetics Synucleinopathy
Compliance with Ethical Standards
Conflict of Interest
Ziv Gan-Or is supported by research grants from the Michael J. Fox Foundation, the Canadian Consortium on Neurodegeneration in Aging (CCNA), the Canadian Glycomics Network (GlycoNet), and the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) program. Dr. Gan-Or is consulting for Sanofi and for Lysosomal Therapeutics Inc. (LTI).
Christopher Liong declares no potential conflicts of interest.
Roy N. Alcalay is supported by the Parkinson’s Disease Foundation, the Michael J. Fox Foundation, and the National Institutes of Health.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance
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