Antidepressants for neuroprotection in Huntington's disease: A review.
Huntington Disease (HD), which is characterized by abnormal dance-like movements, is a neurodegenerative disorder caused by a genetic mutation that results in an expanded polyglutamine stretch in the NH2 terminus of huntingtin protein (HTT). The principal neuropathological hallmarks of disease include loss of striatal and cortical projection neurons. HTT is ubiquitously expressed and is implicated in several cellular functions including neurogenesis, cell trafficking and brain-derived neurotrophic factor (BDNF) production. Major depression is the most common symptom among pre-symptomatic HD carriers and numerous pieces of preclinical evidence have suggested the use of antidepressants in HD not only elevates mood but also slows down the disease progression by activating different neuroprotective mechanism like BDNF/TrkB pathway, MAPK/ERK signalling, neurogenesis and Wnt signalling. HTT plays major role in neurogenesis, a physiological phenomenon that is implicated in some of the behavioral effects of antidepressants. Currently, there is no clinically available treatment that can halt or slow down the progression of HD except tetrabenazine (the only FDA approved drug); however, this drug also induces depression and sedation in patients. In this review, a brief discussion has been made about the mutant HTT that induced various cellular and molecular mechanisms underlying behavioral disorders in HD. Further, an attempt has been made to understand the various cellular mechanisms involved in mediating the neuroprotective effects of antidepressants in HD.
Neuropharmacology Division, I. S. F. College of Pharmacy, Moga 142001, Punjab, India; Research Scholar, I. K. Gujral Punjab Technical University, Jalandhar, Punjab, India.
Sumit
S
Jamwal
Neuropharmacology Division, I. S. F. College of Pharmacy, Moga 142001, Punjab, India. Electronic address: punnubansal79@gmail.com.
Puneet
P
Kumar
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use
D000928:Antidepressive Agents; D018696:Neuroprotective Agents
Antidepressants; Brain derived neurotrophic factor; Huntingtin protein; Huntington's disease; MAPK–ERK signalling; Wnt-GSK-3β Signalling