The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders
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The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders. / Tarafdar, Anuradha; Pula, Giordano.
In: INT J MOL SCI, Vol. 19, No. 12, 30.11.2018.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders
AU - Tarafdar, Anuradha
AU - Pula, Giordano
PY - 2018/11/30
Y1 - 2018/11/30
N2 - For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91phox and was considered to be a peculiarity of professional phagocytic cells. Over the last decade, several more homologs have been identified and based on current research, the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 enzymes. NOXs are electron transporting membrane proteins that are responsible for reactive oxygen species (ROS) generation-primarily superoxide anion (O₂●-), although hydrogen peroxide (H₂O₂) can also be generated. Elevated ROS leads to oxidative stress (OS), which has been associated with a myriad of inflammatory and degenerative pathologies. Interestingly, OS is also the commonality in the pathophysiology of neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). NOX enzymes are expressed in neurons, glial cells and cerebrovascular endothelial cells. NOX-mediated OS is identified as one of the main causes of cerebrovascular damage in neurodegenerative diseases. In this review, we will discuss recent developments in our understanding of the mechanisms linking NOX activity, OS and neurodegenerative diseases, with particular focus on the neurovascular component of these conditions. We conclude highlighting current challenges and future opportunities to combat age-related neurodegenerative disorders by targeting NOXs.
AB - For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91phox and was considered to be a peculiarity of professional phagocytic cells. Over the last decade, several more homologs have been identified and based on current research, the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 enzymes. NOXs are electron transporting membrane proteins that are responsible for reactive oxygen species (ROS) generation-primarily superoxide anion (O₂●-), although hydrogen peroxide (H₂O₂) can also be generated. Elevated ROS leads to oxidative stress (OS), which has been associated with a myriad of inflammatory and degenerative pathologies. Interestingly, OS is also the commonality in the pathophysiology of neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). NOX enzymes are expressed in neurons, glial cells and cerebrovascular endothelial cells. NOX-mediated OS is identified as one of the main causes of cerebrovascular damage in neurodegenerative diseases. In this review, we will discuss recent developments in our understanding of the mechanisms linking NOX activity, OS and neurodegenerative diseases, with particular focus on the neurovascular component of these conditions. We conclude highlighting current challenges and future opportunities to combat age-related neurodegenerative disorders by targeting NOXs.
KW - Amyloid beta-Peptides/metabolism
KW - Animals
KW - Humans
KW - NADPH Oxidases/metabolism
KW - Neurodegenerative Diseases/metabolism
KW - Oxidative Stress/physiology
KW - Reactive Oxygen Species/metabolism
U2 - 10.3390/ijms19123824
DO - 10.3390/ijms19123824
M3 - SCORING: Review article
C2 - 30513656
VL - 19
JO - INT J MOL SCI
JF - INT J MOL SCI
SN - 1661-6596
IS - 12
ER -