Title:C-terminus of Hsp70 Interacting Protein (CHIP) and Neurodegeneration: Lessons from the Bench and Bedside
Volume: 19
Issue: 7
Author(s): Sivakami Mylvaganam, Rebecca Earnshaw, Gregory Heymann, Suneil K. Kalia and Lorraine V. Kalia*
Affiliation:
- Department of Medicine, University of Toronto, Toronto,Canada
Keywords:
Alzheimer's disease, amyotrophic lateral sclerosis, cerebellar ataxia, huntington disease, neurodegenerative diseases,
parkinson's disease, polyglutamine diseases, STUB1, STUB1-associated disease.
Abstract: Neurodegenerative diseases are characterized by the increasing dysfunction and death of
neurons, resulting in progressive impairment of a person’s mobility and/or cognition. Protein misfolding
and aggregation are commonly hypothesized to cause neurotoxicity and, eventually, neuronal
degeneration that are associated with these diseases. Emerging experimental evidence, as well as
recent findings from human studies, reveal that the C-terminus of Hsp70 Interacting Protein
(CHIP), or STIP1 Homology and U-box containing Protein 1 (STUB1), is a quality control protein
involved in neurodegeneration. Here, we review evidence that CHIP interacts with and plays a role
in regulating proteins implicated in the pathogenesis of Parkinson’s disease, Alzheimer’s disease,
amyotrophic lateral sclerosis, and polyglutamine diseases, including Huntington’s disease and
spinocerebellar ataxias. We also review clinical findings identifying mutations in STUB1 as a cause
of both autosomal recessive and autosomal dominant forms of cerebellar ataxia. We propose that
CHIP modulation may have therapeutic potential for the treatment of multiple neurodegenerative
diseases.
