TY - JOUR
T1 - Therapeutic Applications of Cysteamine and Cystamine in Neurodegenerative and Neuropsychiatric Diseases
AU - Paul, Bindu D.
AU - Snyder, Solomon H.
N1 - Funding Information:
Funding. This work was supported by the US Public Health Service grants MH18501 and DA000266 to SS.
Funding Information:
This work was supported by the US Public Health Service grants MH18501 and DA000266 to SS.
Publisher Copyright:
© Copyright © 2019 Paul and Snyder.
PY - 2019/12/12
Y1 - 2019/12/12
N2 - 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.
AB - 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.
KW - BDNF
KW - brain
KW - cystamine
KW - cysteamine
KW - cysteine
KW - neurodegeneration
KW - neuropsychiatric disorder
KW - redox
UR - http://www.scopus.com/inward/record.url?scp=85077285542&partnerID=8YFLogxK
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U2 - 10.3389/fneur.2019.01315
DO - 10.3389/fneur.2019.01315
M3 - Review article
C2 - 31920936
AN - SCOPUS:85077285542
SN - 1664-2295
VL - 10
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 1315
ER -