Dataset Information

Nrf2--a therapeutic target for the treatment of neurodegenerative diseases.

ABSTRACT: The brain is very sensitive to changes in redox status; thus maintaining redox homeostasis in the brain is critical for the prevention of accumulating oxidative damage. Aging is the primary risk factor for developing neurodegenerative diseases. In addition to age, genetic and environmental risk factors have also been associated with disease development. The primary reactive insults associated with the aging process are a result of oxidative stress (OS) and nitrosative stress (NS). Markers of increased oxidative stress, protein and DNA modification, inflammation, and dysfunctional proteostasis have all been implicated in contributing to the progression of neurodegeneration. The ability of the cell to combat OS/NS and maintain a clearance mechanism for misfolded aggregating proteins determines whether or not it will survive. A critical pathway in this regard is the Nrf2 (nuclear factor erythroid 2-related factor 2)- antioxidant response element (ARE) pathway. Nrf2 activation has been shown to mitigate a number of pathologic mechanisms associated with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. This review will focus on the role of Nrf2 in these diseases and the potential for Nrf2 activation to attenuate disease progression.

SUBMITTER: Johnson DA

PROVIDER: S-EPMC4809057 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nrf2--a therapeutic target for the treatment of neurodegenerative diseases.

Johnson Delinda A DA Johnson Jeffrey A JA

Free radical biology & medicine 20150814 Pt B

The brain is very sensitive to changes in redox status; thus maintaining redox homeostasis in the brain is critical for the prevention of accumulating oxidative damage. Aging is the primary risk factor for developing neurodegenerative diseases. In addition to age, genetic and environmental risk factors have also been associated with disease development. The primary reactive insults associated with the aging process are a result of oxidative stress (OS) and nitrosative stress (NS). Markers of inc ...[more]

PMID: 26281945

Similar Datasets

Project description:Abstract Neurosecretory protein VGF (non-acronymic) belongs to the granin family of neuropeptides. VGF and VGF-derived peptides have been repeatedly identified in well-powered and well-designed multi-omic studies as dysregulated in neurodegenerative and psychiatric diseases. New therapeutics is urgently needed for these devastating and costly diseases, as are new biomarkers to improve disease diagnosis and mechanistic understanding. From a list of 537 genes involved in Alzheimer’s disease pathogenesis, VGF was highlighted by the Accelerating Medicines Partnership in Alzheimer’s disease as the potential therapeutic target of greatest interest. VGF levels are consistently decreased in brain tissue and CSF samples from patients with Alzheimer’s disease compared to controls, and its levels correlate with disease severity and Alzheimer’s disease pathology. In the brain, VGF exists as multiple functional VGF-derived peptides. Full-length human VGF1–615 undergoes proteolytic processing by prohormone convertases and other proteases in the regulated secretory pathway to produce at least 12 active VGF-derived peptides. In cell and animal models, these VGF-derived peptides have been linked to energy balance regulation, neurogenesis, synaptogenesis, learning and memory, and depression-related behaviours throughout development and adulthood. The C-terminal VGF-derived peptides, TLQP-62 (VGF554–615) and TLQP-21 (VGF554–574) have differential effects on Alzheimer’s disease pathogenesis, neuronal and microglial activity, and learning and memory. TLQP-62 activates neuronal cell-surface receptors and regulates long-term hippocampal memory formation. TLQP-62 also prevents immune-mediated memory impairment, depression-like and anxiety-like behaviours in mice. TLQP-21 binds to microglial cell-surface receptors, triggering microglial chemotaxis and phagocytosis. These actions were reported to reduce amyloid-β plaques and decrease neuritic dystrophy in a transgenic mouse model of familial Alzheimer’s disease. Expression differences of VGF-derived peptides have also been associated with frontotemporal lobar dementias, amyotrophic lateral sclerosis, Lewy body diseases, Huntington’s disease, pain, schizophrenia, bipolar disorder, depression and antidepressant response. This review summarizes current knowledge and highlights questions for future investigation regarding the roles of VGF and its dysregulation in neurodegenerative and psychiatric disease. Finally, the potential of VGF and VGF-derived peptides as biomarkers and novel therapeutic targets for neurodegenerative and psychiatric diseases is highlighted. Quinn et al. summarizes the physiological role of the neuropeptide VGF and VGF-derived peptides in brain and behaviour alongside their dysregulation and role in neurodegenerative and psychiatric disease. Finally, the potential use of VGF and VGF-derived peptides as biomarkers and therapeutic targets of neurodegenerative and psychiatric diseases is highlighted. <Please insert Graphical abstract here> Graphical Abstract Graphical Abstract

Dataset Information

Nrf2--a therapeutic target for the treatment of neurodegenerative diseases.

Publications

Nrf2--a therapeutic target for the treatment of neurodegenerative diseases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets