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Review
. 2019 Dec 12;10:1315.
doi: 10.3389/fneur.2019.01315. eCollection 2019.

Therapeutic Applications of Cysteamine and Cystamine in Neurodegenerative and Neuropsychiatric Diseases

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Free PMC article
Review

Therapeutic Applications of Cysteamine and Cystamine in Neurodegenerative and Neuropsychiatric Diseases

Bindu D Paul et al. Front Neurol. .
Free PMC article

Abstract

Current medications for neurodegenerative and neuropsychiatric diseases such as Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), and Schizophrenia mainly target disease symptoms. Thus, there is an urgent need to develop novel therapeutics that can delay, halt or reverse disease progression. AD, HD, PD, and schizophrenia are characterized by elevated oxidative and nitrosative stress, which play a central role in pathogenesis. Clinical trials utilizing antioxidants to counter disease progression have largely been unsuccessful. Most antioxidants are relatively non-specific and do not adequately target neuroprotective pathways. Accordingly, a search for agents that restore redox balance as well as halt or reverse neuronal loss is underway. The small molecules, cysteamine, the decarboxylated derivative of the amino acid cysteine, and cystamine, the oxidized form of cysteamine, respectively, mitigate oxidative stress and inflammation and upregulate neuroprotective pathways involving brain-derived neurotrophic factor (BDNF) and Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Cysteamine can traverse the blood brain barrier, a desirable characteristic of drugs targeting neurodegeneration. This review addresses recent developments in the use of these aminothiols to counter neurodegeneration and neuropsychiatric deficits.

Keywords: BDNF; brain; cystamine; cysteamine; cysteine; neurodegeneration; neuropsychiatric disorder; redox.

Figures

Figure 1
Figure 1
(A) Biosynthesis of cysteamine and intersection with cysteine catabolism. Cysteamine is generated in mammals by the degradation of coenzyme A, which is required for the metabolism of fatty acids, carbohydrates, amino acids and ketone bodies. When coenzyme A is cleaved (cleavage at the dotted line), pantetheine is generated, which is acted on by pantetheinase or vanin to form cysteamine. Cysteamine is converted to hypotaurine by cysteamine decarboxylase. Cysteine, a component of coenzyme A, is acted on by cysteine dioxygenase to form cysteine sulfonate which is decarboxylated by cysteine sulfonate decarboxylase to form hypotaurine. Hypotaurine generated is further metabolized to taurine by hypotaurine decarboxylase. (B) Effects of cysteamine/cystamine. Both cysteamine and its oxidized form cystamine have protective effects in cells and tissues. Originally identified as radioprotective molecules, subsequently these aminothiols have been reported to mitigate cystinosis, a condition characterized by accumulation of cystine crystals in the body. Cystamine and cysteamine have a variety of other effects which include antioxidant effects (by increasing cysteine and glutathione levels), inhibition of transglutaminase 2 and caspase 3 (possibly by modifying reactive cysteine residues or cysteaminylation), modulation of mitochondrial function, immunomodulation. These molecules have also been reported to increase levels of brain derived neurotrophic factor (BDNF) and heat shock proteins, which affords neuroprotective benefits.

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