Figure caption:
Schematic representation of the diverse pathways regulated by TIP60. TIP60 regulates diverse cellular pathways including autophagy, DNA repair, neuronal survival, learning/memory, sleep/wake patterns, and protein turnover, all of which contribute to cellular homeostasis and organismal health so as to counteract aging and neurodegeneration.
TIP60 in aging and neurodegeneration
Ageing research reviews, 2020
DOI: 10.1016/j.arr.2020.101195
Epigenetic modification of chromatin, including histone methylation and acetylation, plays critical roles in eukaryotic cells and has a significant impact on chromatin structure/accessibility, gene regulation and, susceptibility to aging, neurodegenerative disease, cancer, and other age-related diseases. This article reviews the current advances on TIP60/KAT5, a major histone acetyltransferase with diverse functions in eukaryotes, with emphasis on its regulation of autophagy, proteasome-dependent protein turnover, RNA transcription, DNA repair, circadian rhythms, learning and memory, and other neurological functions implicated in aging and neurodegeneration. Moreover, the promising therapeutic potential of TIP60 is discussed to target Alzheimer’s disease and other neurological diseases.
Drosophila models for in vivo studies of the neurobiological roles of TIP60. Fundamental properties of the Drosophila model system for studying neurobiological roles of TIP60 are shown. The fly CNS contains the brain and ventral nerve cord (VNC). The brain mushroom body (MB) is the central region for cognitive processing, while the pacemaker cells, sLNvs/lLNvs, are suitable for studying the sleep/wake cycle in flies. Peripheral motor neurons are useful for studying neuronal development. The innervation between muscle 6 and 7 in the larva and that between indirect flight muscles (IFMs) in the adult forming the neuromuscular junction (NMJ) are useful for studying synapses and synaptic transmission. D, dorsal; V, ventral; A, anterior; P, posterior; M, medial; L, lateral. PI, pars intercerebralis. Ca, calyx. sLNvs, small ventrolateral neurons; lLNvs, large ventrolateral neurons. Mushroom body lobes: α/β, α’/β’, and γ neurons.