This article is part of the supplement: Ubiquitin-Proteasome System in Disease Part 1

Review

Role of the ubiquitin proteasome system in Alzheimer's disease

Sudarshan C Upadhya¹ and Ashok N Hegde^1,

¹Department of Neurobiology and Anatomy, Wake Forest University Health Sciences Medical Center Boulevard, Winston-Salem, NC 27157, USA

author email corresponding author email

BMC Biochemistry 2007, 8(Suppl 1):S12doi:10.1186/1471-2091-8-S1-S12

Published:	22 November 2007

Abstract

Though Alzheimer's disease (AD) is a syndrome with well-defined clinical and neuropathological manifestations, an array of molecular defects underlies its pathology. A role for the ubiquitin proteasome system (UPS) was suspected in the pathogenesis of AD since the presence of ubiquitin immunoreactivity in AD-related neuronal inclusions, such as neurofibrillary tangles, is seen in all AD cases. Recent studies have indicated that components of the UPS could be linked to the early phase of AD, which is marked by synaptic dysfunction, as well as to the late stages of the disease, characterized by neurodegeneration. Insoluble protein aggregates in the brain of AD patients could result from malfunction or overload of the UPS, or from structural changes in the protein substrates, which prevent their recognition and degradation by the UPS. Defective proteolysis could cause the synaptic dysfunction observed early in AD since the UPS is known to play a role in the normal functioning of synapses. In this review, we discuss recent observations on possible links between the UPS and AD, and the potential for utilizing UPS components as targets for treatment of this disease.

Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com webcite).