HINT1 in Neuropsychiatric Diseases: A Potential Neuroplastic Mediator

Abstract

Although many studies have investigated the functions of histidine triad nucleotide-binding protein 1 (HINT1), its roles in neurobiological processes remain to be fully elucidated. As a member of the histidine triad (HIT) enzyme superfamily, HINT1 is distributed in almost every organ and has both enzymatic and nonenzymatic activity. Accumulating clinical and preclinical evidence suggests that HINT1 may play an important role as a neuroplastic mediator in neuropsychiatric diseases, such as schizophrenia, inherited peripheral neuropathies, mood disorders, and drug addiction. Though our knowledge of HINT1 is limited, it is believed that further research on the neuropathological functions of HINT1 would eventually benefit patients with neuropsychiatric and even psychosomatic diseases.

The role of HINT1 protein in morphine addiction: An animal model‐based study

“…Studies have shown that HINT1 is involved in a variety of neuropsychiatric disorders, including drug addiction 13, 20 . Recent studies have shown a genetic association between HINT1 and nicotine dependence.…”

“…Nicotine enters the body and regulates HINT1, which in turn may be related to the nicotine addiction process 22 . However, as of now, there is no direct study on the role of HINT1 in morphine addiction 13, 20, 23 …”

“…HINT1 protein is widely distributed in the mouse central nervous system (CNS) 12 . In fact, HINT1 is involved in a variety of mental disorders such as schizophrenia, pain, and drug dependence 13 . Studies have confirmed that there is a genetic association between HINT1 and the dependence of nicotine and cocaine 13 .…”

“…In fact, HINT1 is involved in a variety of mental disorders such as schizophrenia, pain, and drug dependence 13 . Studies have confirmed that there is a genetic association between HINT1 and the dependence of nicotine and cocaine 13 . However, there is currently no direct research on the role of HINT1 protein in morphine addiction at home and abroad.…”

Broad kinase inhibition mitigates early neuronal dysfunction and cognitive deficits in tauopathy

“…HINT1, or histidine triad nucleotide-binding protein 1, was originally described as a protein kinase regulator, but has more recently been implicated in regulation of G protein coupled receptors, or GPCRs, as well as transcription factors that influence Wnt/beta-catenin signaling (91)(92)(93)(94). HINT1 has been implicated in many neuropsychiatric disorders including schizophrenia, mood disorders, and drug addiction (95). In Schizophrenia, HINT1 is downregulated in both the dorsolateral prefrontal cortex and prefrontal cortex (96,97), which mirror its abundance in AD.…”