TY - JOUR
T1 - Neurodegeneration
T2 - Impact of S-nitrosylated Parkin, DJ-1 and PINK1 on the pathogenesis of Parkinson's disease
AU - Sircar, Esha
AU - Rai, Sristi Raj
AU - Wilson, Mark A.
AU - Schlossmacher, Michael G.
AU - Sengupta, Rajib
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6/15
Y1 - 2021/6/15
N2 - Parkinson's disease (PD) is one of the fastest-growing neurodegenerative disorders of increasing global prevalence. It represents the second most common movement disorder after tremor and the second most common neurodegenerative disorder after Alzheimer's disease. The incidence rate of idiopathic PD increases steadily with age, however, some variants of autosomal recessive inheritance are present with an early age-at-onset (ARPD). Approximately 50 percent of ARPD cases have been linked to bi-allelic mutations in genes encoding Parkin, DJ-1, and PINK1. Each protein has been implicated in maintaining proper mitochondrial function, which is particularly important for neuronal health. Aberrant post-translational modifications of these proteins may disrupt their cellular functions and thus contributing to the development of idiopathic PD. Some post-translational modifictions can be attributed to the dysregulation of potentially harmful reactive oxygen and nitrogen species inside the cell, which promote oxidative and nitrosative stress, respectively. Unlike oxidative modifications, the covalent modification by Nitric Oxide under nitrosative stress, leading to S-nitrosylation of Parkin, DJ-1; and PINK1, is less studied. Here, we review the available literature on S-nitrosylation of these three proteins, their implications in the pathogenesis of PD, and provide an overview of currently known, denitrosylating systems in eukaryotic cells.
AB - Parkinson's disease (PD) is one of the fastest-growing neurodegenerative disorders of increasing global prevalence. It represents the second most common movement disorder after tremor and the second most common neurodegenerative disorder after Alzheimer's disease. The incidence rate of idiopathic PD increases steadily with age, however, some variants of autosomal recessive inheritance are present with an early age-at-onset (ARPD). Approximately 50 percent of ARPD cases have been linked to bi-allelic mutations in genes encoding Parkin, DJ-1, and PINK1. Each protein has been implicated in maintaining proper mitochondrial function, which is particularly important for neuronal health. Aberrant post-translational modifications of these proteins may disrupt their cellular functions and thus contributing to the development of idiopathic PD. Some post-translational modifictions can be attributed to the dysregulation of potentially harmful reactive oxygen and nitrogen species inside the cell, which promote oxidative and nitrosative stress, respectively. Unlike oxidative modifications, the covalent modification by Nitric Oxide under nitrosative stress, leading to S-nitrosylation of Parkin, DJ-1; and PINK1, is less studied. Here, we review the available literature on S-nitrosylation of these three proteins, their implications in the pathogenesis of PD, and provide an overview of currently known, denitrosylating systems in eukaryotic cells.
KW - Glutaredoxin
KW - PINK1
KW - Parkin, DJ-1
KW - Parkinson's disease
KW - S-nitrosylation
KW - Thioredoxin
UR - http://www.scopus.com/inward/record.url?scp=85103927056&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103927056&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2021.108869
DO - 10.1016/j.abb.2021.108869
M3 - Review article
C2 - 33819447
AN - SCOPUS:85103927056
SN - 0003-9861
VL - 704
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
M1 - 108869
ER -