Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders

Abstract

Reactive species play an important role in physiological functions. Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species along with the failure of balance by the body’s antioxidant enzyme systems results in destruction of cellular structures, lipids, proteins, and genetic materials such as DNA and RNA. Moreover, the effects of reactive species on mitochondria and their metabolic processes eventually cause a rise in ROS/RNS levels, leading to oxidation of mitochondrial proteins, lipids, and DNA. Oxidative stress has been considered to be linked to the etiology of many diseases, including neurodegenerative diseases (NDDs) such as Alzheimer diseases, Amyotrophic lateral sclerosis, Friedreich’s ataxia, Huntington’s disease, Multiple sclerosis, and Parkinson’s diseases. In addition, oxidative stress causing protein misfold may turn to other NDDs include Creutzfeldt-Jakob disease, Bovine Spongiform Encephalopathy, Kuru, Gerstmann-Straussler-Scheinker syndrome, and Fatal Familial Insomnia. An overview of the oxidative stress and mitochondrial dysfunction-linked NDDs has been summarized in this review.

Keywords:

• Neurodegenerative diseases
• oxidative stress
• mitochondrial dysfunction

Abbreviations:

• AD: Alzheimer’s disease
• ALS: Amyotrophic lateral sclerosis
• Aβ: amyloid-β
• AP-1: activator protein 1
• APP: Aβ precursor protein
• BBB: blood–brain barrier
• BER: base excision repair
• BSE: Bovine Spongiform Encephalopathy
• CAA: cerebral amyloid angiopathy
• CAT: catalase
• CBF: cerebral blood flow
• CJD: Creutzfeldt-Jakob disease
• CNS: central nervous system
• COX: cyclooxygenase
• CRP: C-reactive protein
• Cyt-c: cytochrome c
• DA: dopamine
• DAG: diacylglycerol
• DJ-1: protein deglycase 1
• DNMT: DNA methyltransferase
• DOPAC: 3, 4-dihydroxyphenylacetic acid
• DRG: dorsal root ganglia
• DSBs: double strand breaks
• EPCs: endothelial progenitor cells
• FFI: Fatal Familial Insomnia
• FRDA: Friedreich’s ataxia
• GPx: glutathione peroxidase
• GSH: glutathione
• GSS: Gerstmann-Straussler-Scheinker syndrome
• HD: Huntington’s disease
• HIF-1α: hypoxia-inducible factor-1 alpha
• HNE: 4- hydroxynonenal
• HVA: homovanillic acid
• IL: interleukin
• iNOS: inducible nitric oxide synthase
• IR: ionizing radiation
• JAK: Janus kinase
• MAO-B: monoamine oxidase B
• MDA: malondialdehyde
• MMPs: matrix metalloproteins
• mtMP: mitochondrial membrane permeability/potential
• mtDNA: mitochondrial DNA
• NADP: nicotinamide adenine dinucleotide phosphate
• NDDs: neurodegenerative diseases
• NFTs: neurofibrillary tangles
• NF-κB: nuclear factor kappa B
• NHEJ: non-homologous end joining
• NHR: nucleotide excision repair
• RNS: reactive nitrogen species
• PD: Parkinson’s disease
• PG: prostaglandin
• PGC-1α: peroxisome proliferator-activated receptor-γ co-activator-1α
• PPL: phospholipase
• PrP: prion protein
• ROS: reactive oxygen species
• SC: spinal cord
• SMCs: smooth muscle cells
• SOD: superoxide dismutase
• SSBs: single strand breaks
• TGF-β: tumor growth factor-beta
• TNF-α: tumor necrosis factor-alpha
• TOMM40: a gene associated with AD
• TSEs: Transmissible Spongiform Encephalopathies
• VEGF: vascular endothelial growth factor

Notes on contributor:

Md. Torequl Islam is currently working as a PhD student at UFPI, Brazil. His current research area is Biotechnology in Natural Products (Drug Discovery & Development). However, he is working with the following keywords: antioxidant; oxidative stress; cancer strategies; antimicrobial agents; cytotoxicity; genotoxicity; mutagenicity; radiation effects; diterpenes; method development; pharmacological screening; nanoformulations; toxicology; risk assessment. As a pharmacist, he has a keen interest in the development of new, safe, and effective anticancer therapy.