Defective proteostasis in Alzheimer?s disease

The homeostasis of cellular proteins, or proteostasis, is critical for neuronal function and for brain processes, including learning and memory. Increasing evidence indicates that defective proteostasis contributes to the progression of neurodegenerative disorders, including Alzheimer's disease (AD), the most prevalent form of dementia in the elderly. Proteostasis comprises a set of cellular mechanisms that control protein synthesis, folding, post-translational modification and degradation, all of which are deregulated in AD. Importantly, deregulation of proteostasis plays a key role in synapse dysfunction and in memory impairment, the major clinical manifestation of AD. Here, we discuss molecular pathways involved in protein synthesis and degradation that are altered in AD, and possible pharmacological approaches to correct these defects.

Automated summary

The homeostasis of cellular proteins, or proteostasis, is crucial for neuronal function and brain processes, including learning and memory. Defective proteostasis has been found to contribute to the progression of Alzheimer's disease, the most common form of dementia in the elderly. This article discusses the molecular pathways involved in protein synthesis and degradation that are altered in Alzheimer's disease, as well as potential pharmacological approaches to correct these defects.