Journal of Alzheimers Disease & Parkinsonism
Open Access

Review Article

Proteostasis and Secondary Proteinopathy in Alzheimer's Disease

David R. Borchelt^1-4*,Guilian Xu^1-4, Lucia Notterpek^1,3, Jada Lewis^1-3

¹ Department of Neuroscience, University of Florida, Gainesville, FL, USA

² Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA

³ McKnight Brain Institute, University of Florida, Gainesville, FL, USA

⁴ SantaFe HealthCare Alzheimer’s Disease Research Center, University of Florida, Gainesville, FL, USA

Corresponding Author:

David R. Borchelt
University of Florida
Gainesville, FL, 32610, USA
Tel: 1-352-273-9664
E-mail: drb1@ufl.edu

Received date: March 12, 2014; Accepted date: April 20, 2014; Published date: May 20, 2014

Citation: Borchelt RD, Xu G, Notterpek L, Lewis J (2014) Proteostasis and Secondary Proteinopathy in Alzheimer’s Disease. J Alzheimers Dis Parkinsonism 4:145. doi: 10.4172/2161-0460.1000145

Copyright: © 2014 Borchelt DR et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

t is now widely recognized that the brains of Alzheimer’s patients often display multiple pathologic abnormalities, termed mixed proteinopathies. These individuals will by definition always have amyloid pathology mixed with neurofibrillary tangles, may also have TDP-43 or α -synuclein pathology. The basis for the preponderance of mixed pathology in Alzheimer’s Disease (AD) is poorly understood, but recent studies have suggested that compromised function of the proteostasis network could be an important contributing factor. The term proteostasis network refers to the myriad of activities and functions that work in concert to maintain the proteome. In settings of neurodegeneration, it is thought that high levels of misfolded proteins produce an added burden on the proteostatic network by occupying various activities required to dissociate such aggregates and degrade the misfolded proteins, leaving vulnerable “by-stander” proteins at greater risk for misfolding and aggregation. In proteomic studies of brains from mice with high levels of Alzheimer-amyloidosis, we have recently determined that a number of cytosolic proteins solubility as amyloid burdens rise. This finding is consistent with the hypothesis that amyloid deposition can, by some manner, impinge on the function of the proteostatic network to cause “secondary” misfolding. Thus, in mice that model human neurodegenerative pathology, evidence is emerging in support of the concept that the accumulation of one misfolded protein can, by some manner, impact on the folding of others