The Peptidyl-prolyl Isomerase Pin1 in Neuronal Signaling: from Neurodevelopment to Neurodegeneration
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The Peptidyl-prolyl Isomerase Pin1 in Neuronal Signaling: from Neurodevelopment to Neurodegeneration Francesca Fagiani 1,2
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Stefano Govoni 1
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Marco Racchi 1
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Cristina Lanni 1
Received: 24 June 2020 / Accepted: 14 October 2020 # The Author(s) 2020
Abstract The peptidyl-prolyl isomerase Pin1 is a unique enzyme catalyzing the isomerization of the peptide bond between phosphorylated serine-proline or threonine-proline motifs in proteins, thereby regulating a wide spectrum of protein functions, including folding, intracellular signaling, transcription, cell cycle progression, and apoptosis. Pin1 has been reported to act as a key molecular switch inducing cell-type-specific effects, critically depending on the different phosphorylation patterns of its targets within different biological contexts. While its implication in proliferating cells, and, in particular, in the field of cancer, has been widely characterized, less is known about Pin1 biological functions in terminally differentiated and post-mitotic neurons. Notably, Pin1 is widely expressed in the central and peripheral nervous system, where it regulates a variety of neuronal processes, including neuronal development, apoptosis, and synaptic activity. However, despite studies reporting the interaction of Pin1 with neuronal substrates or its involvement in specific signaling pathways, a more comprehensive understanding of its biological functions at neuronal level is still lacking. Besides its implication in physiological processes, a growing body of evidence suggests the crucial involvement of Pin1 in aging and age-related and neurodegenerative diseases, including Alzheimer’s disease, Parkinson disease, frontotemporal dementias, Huntington disease, and amyotrophic lateral sclerosis, where it mediates profoundly different effects, ranging from neuroprotective to neurotoxic. Therefore, a more detailed understanding of Pin1 neuronal functions may provide relevant information on the consequences of Pin1 deregulation in age-related and neurodegenerative disorders. Keywords Pin1 . Neurodevelopment . Neurodegeneration . Neuronal apoptosis . Alzheimer’s disease
Background The Peptidyl-prolyl Isomerase Pin1 Discovered in 1996 as a protein associating with NIMA (never in mitosis) regulating mitosis [1], the peptidyl-prolyl Francesca Fagiani and Stefano Govoni contributed equally to this work. * Cristina Lanni [email protected] Francesca Fagiani [email protected] Stefano Govoni [email protected] Marco Racchi [email protected] 1
Department of Drug Sciences, Pharmacology Section, University of Pavia, Viale Taramelli 14, 27100 Pavia, Italy
2
Scuola Universitaria Superiore IUSS Pavia, P.zza Vittoria, 15, 27100 Pavia, Italy
isomerase Pin1 (protein interacting with NIMA-1) is an ubiquitously expressed cis/trans isomerase targeting the phosphorylated serine-proline (pSer-Pro) or threonine-proline (pThrPro) motifs [1], belonging to the evolutionarily conserved family of PPIase (peptidyl-prolyl cis/trans isomerase). The WW domain on the N-terminus spec
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