Alzheimer’s Disease and Proteasome: The Therapeutic Development and Management
Pp. 99-139 (41)
Qunxing Ding and Haiyan Zhu
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.
Aging, Alzheimer’s disease, Clinical trial, Immune, Management,
Neurodegeneration, Pharmaceutical development, Proteasome, Subunits.
Department of Biological Sciences, Kent State University, East Liverpool, OH, USA.