Alzheimer’s Disease and Proteasome: The Therapeutic Development and Management

The proteasome system is a cellular machinery that is responsible for the degradation of nearly 90% of the proteins in cells and is crucial in protein metabolism involved in physiological and pathological developments, especially in aging and aging-related disorders. Numerous reports indicate that impaired proteasome is involved in the pathological process of Alzheimer’s disease (AD), which is a leading form of dementia. It is well known that the pathological hallmarks of the AD are the aggregated proteins such as plaques, tangles and Lewy bodies. The formation of these aggregates is tightly associated with the dysfunction of the proteasome system, which is responsible for the degradation of oxidized, misfolded, aged and other damaged proteins. In fact, the proteasome system plays a major role in quality and quantity control in cellular protein homeostasis, and in responses to inflammatory signals, oxidative stress, and other cellular signals. This chapter will summarize the basic information and updates on the proteasome system and related cellular complexes, such as lysosome and ribosome and their alterations during aging and AD pathogenesis. In addition, some clinical trials and practical management for the AD will be discussed to explore possible strategies for pharmaceutical and clinical development associated with the proteasome system.

Keywords: Aging, Alzheimer’s disease, Clinical trial, Immune, Management, Neurodegeneration, Pharmaceutical development, Proteasome, Subunits.