Phosphorylation-specific peptidyl-prolyl isomerization of neuronal cytoskeletal proteins by Pin1: implications for therapeutics in neurodegeneration

Journal of Alzheimer's Disease : JAD
Parvathi Rudrabhatla, Harish C Pant

Abstract

Pin1 [Protein Interacting with NIMA (never in mitosis A)] is a peptidyl prolyl cis-trans isomerase that isomerizes phospho-Serine/Threonine-Proline [p(S/T)-P] motifs of its target proteins. Pin1 functions in concert with proline directed kinases such as cyclin-dependent protein kinases, extracellular signal-regulated kinases, and c-Jun N- terminal kinase, and protein phosphatases such as protein phosphatase 2A (PP2A) and PP2B, in the regulation of a wide range of cellular processes including cell division, DNA damage response, and gene transcription, and in susceptibility to cancer and neurodegenerative diseases. This review focuses on the roles of Pin1 in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Frontotemporal dementia associated with parkinsonism linked to chromosome 17. Pin1 interacts with neuronal cytoskeletal proteins such as tau, amyloid-beta protein precursor, alpha-synuclein, and neurofilaments, often in association with phosphorylation events that influence their functions in the neuronal cytoskeleton. Overexpression of Pin1 reduces WT tau stability but increases P301L mutant tau stability. Pin1 associates with neurofilament H (NF-H) and modulate...Continue Reading

Citations

Nov 27, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Parvathi RudrabhatlaHarish C Pant
May 31, 2014·BioMed Research International·Beatrice ArosioDaniela Mari
May 2, 2014·Frontiers in Cellular Neuroscience·Paola ZacchiEnrico Cherubini
Feb 28, 2017·Neurochemical Research·Lan TangBinglin Zhu
Jun 26, 2014·Neuropathology and Applied Neurobiology·Uwe UeberhamThomas Arendt
Apr 2, 2020·Cell Biochemistry and Function·Fatemeh HadiMohammad R Fattahi
Feb 12, 2021·Cerebral Cortex·Xiaojun HouHekun Liu
Apr 20, 2011·Journal of Cell Science·Claire L HyderJohn E Eriksson
Feb 5, 2014·Chemical Reviews·Michal Szostak, Jeffrey Aubé

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