TY - JOUR
T1 - Poly (ADP-ribose) polymerase 1 and Parkinson's disease
T2 - A study in post-mortem human brain
AU - Salemi, Michele
AU - Mazzetti, Samanta
AU - De Leonardis, Mara
AU - Giampietro, Federica
AU - Medici, Valentina
AU - Poloni, Tino Emanuele
AU - Cannarella, Rossella
AU - Giaccone, Giorgio
AU - Pezzoli, Gianni
AU - Cappelletti, Graziella
AU - Ferri, Raffaele
N1 - Funding Information:
This study was supported by the Italian “5 x 1000” funding.
Publisher Copyright:
© 2021
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - Poly (ADP-ribose) polymerase 1 (PARP1) is crucial in both maintenance of genome integrity and cell death. PARP1 activation has been very recently linked to Parkinson's disease (PD) and its role in inducing the pathologic accumulation of α-Synuclein demonstrated in a PD mouse model. The objective of this study was to investigate the presence and localization of PARP1 in PD brain. PARP1 localization was assessed by immunostaining and confocal microscopy in post-mortem human brains obtained from PD patients (Braak stage VI) compared to controls. PARP1 positive nuclei in substantia nigra, mainly in dopaminergic neurons but also in astrocytes and oligodendrocytes, were decreased in PD. The same alteration was observed in several areas that are affected in PD pathology, namely the dorsal motor nucleus of vagus, frontal and cingulate cortex, whereas no changes in PARP1 staining were detectable in the inferior olivary nucleus that is unaffected in PD. In addition, PARP1 co-localizes with α-Synuclein that is accumulated in the cytoplasm and in Lewy bodies of PD tissue sections. Our data reveal previously unknown changes of PARP1 localization in the brain of PD patients, in both neurons and glia, supporting its widespread involvement in this pathology and its potential use as a therapeutic target.
AB - Poly (ADP-ribose) polymerase 1 (PARP1) is crucial in both maintenance of genome integrity and cell death. PARP1 activation has been very recently linked to Parkinson's disease (PD) and its role in inducing the pathologic accumulation of α-Synuclein demonstrated in a PD mouse model. The objective of this study was to investigate the presence and localization of PARP1 in PD brain. PARP1 localization was assessed by immunostaining and confocal microscopy in post-mortem human brains obtained from PD patients (Braak stage VI) compared to controls. PARP1 positive nuclei in substantia nigra, mainly in dopaminergic neurons but also in astrocytes and oligodendrocytes, were decreased in PD. The same alteration was observed in several areas that are affected in PD pathology, namely the dorsal motor nucleus of vagus, frontal and cingulate cortex, whereas no changes in PARP1 staining were detectable in the inferior olivary nucleus that is unaffected in PD. In addition, PARP1 co-localizes with α-Synuclein that is accumulated in the cytoplasm and in Lewy bodies of PD tissue sections. Our data reveal previously unknown changes of PARP1 localization in the brain of PD patients, in both neurons and glia, supporting its widespread involvement in this pathology and its potential use as a therapeutic target.
KW - Alpha-synuclein
KW - Human brain
KW - Neurodegeneration
KW - Parkinson's disease
KW - PARP1
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U2 - 10.1016/j.neuint.2021.104978
DO - 10.1016/j.neuint.2021.104978
M3 - Article
AN - SCOPUS:85100426566
SN - 0197-0186
VL - 144
JO - Neurochemistry International
JF - Neurochemistry International
M1 - 104978
ER -