Kanisa Davidson

1 Introduction Declines in proteasome function are a robust feature of aging reported in a wide range of tissues in mice (Bardag-Gorce et al. 1999; Keller, Hanni, and Markesbery 2000; Rodriguez, Gaczynska, and Osmulski 2010), including the nervous system (Keller, Hanni, and Markesbery 2000). Similar declines are observed in the heads of fruit flies (Munkacsy et al. 2019) and the brains of killifish (Kelmer Sacramento et al. 2020).

Abstract Background: Alzheimers Disease (AD) is the leading cause of dementia globally, affecting around 50 million people and marked by cognitive decline and the accumulation of β-amyloid plaques and hyperphosphorylated tau. The limited treatment options and numerous failed clinical trials targeting β-amyloid (Aβ) highlight the need for novel approaches. Lowered proteasome activity is a consistent feature in AD, particularly in the hippocampus.

Publication Date 1-1-2023 Journal Frontiers in Cell and Development Biology Abstract The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays critical roles in nervous system processes. This includes maintenance of cellular homeostasis in neurons. It also includes roles in long-term potentiation via modulation of CREB signaling.