Neurodegenerative Diseases as Protein Folding Disorders
Document Type
Book Chapter
Publication Date
2018
Keywords
Protein Aggregation, Misfolding, Neurodegeneration, Amyloid Fibril, Oligomer, Alzheimer’s, Dementia
Digital Object Identifier (DOI)
https://doi.org/10.1016/B978-0-12-811304-2.00009-2
Abstract
This chapter focuses on the misbehavior of key proteins that are aberrantly misfolded or misassembled, leading to neuronal loss producing motor or cognitive impairments found in many neurological disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. These amyloid aggregates are distinguished by characteristic β-sheet structures that can form long fibrils as well as recruit and convert protein that has not yet misfolded. Indeed, because amyloid formation results in a heterogeneous mix of many oligomeric, prefibrillar, and fibrillar structures, determining the toxic aggregated species has been difficult, and current therapeutics have failed to prevent the pathology caused by these proteins. Here we provide background on protein folding regulatory processes as well as illustrate certain determinants for protein misfolding. We will also describe current hypotheses on how protein aggregates cause cellular stress and neurodegeneration and provide an overview of new early detection and therapeutic strategies.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Neurodegenerative Diseases as Protein Folding Disorders, in M. S. Wolfe (Ed.), The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms, Academic Press, p. 243-267
Scholar Commons Citation
Baker, Jeremy D.; Webster, Jack M.; Shelton, Lindsey B.; Koren, John III; Uversky, Vladimir N.; Blair, Laura J.; and Dickey, Chad A., "Neurodegenerative Diseases as Protein Folding Disorders" (2018). Molecular Medicine Faculty Publications. 1096.
https://digitalcommons.usf.edu/mme_facpub/1096
