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PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes.

ABSTRACT: Receptor-type protein tyrosine phosphatase, receptor type D (PTPRD) has likely roles as a neuronal cell adhesion molecule and synaptic specifier. Interest in its neurobiology and genomics has been stimulated by results from human genetics and mouse models for phenotypes related to addiction, restless leg syndrome, neurofibrillary pathology in Alzheimer's disease, cognitive impairment/intellectual disability, mood lability, and obsessive-compulsive disorder. We review PTPRD's discovery, gene family, candidate homomeric and heteromeric binding partners, phosphatase activities, brain distribution, human genetic associations with nervous system phenotypes, and mouse model data relevant to these phenotypes. We discuss the recently reported discovery of the first small molecule inhibitor of PTPRD phosphatase, the identification of its addiction-related effects, and the implications of these findings for the PTPRD-associated brain phenotypes. In assembling PTPRD neurobiology, human genetics, and mouse genetic and pharmacological datasets, we provide a compelling picture of the roles played by PTPRD, its variation, and its potential as a target for novel therapeutics.

SUBMITTER: Uhl GR

PROVIDER: S-EPMC6629525 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes.

Uhl George R GR Martinez Maria J MJ

Annals of the New York Academy of Sciences 20190115 1

Receptor-type protein tyrosine phosphatase, receptor type D (PTPRD) has likely roles as a neuronal cell adhesion molecule and synaptic specifier. Interest in its neurobiology and genomics has been stimulated by results from human genetics and mouse models for phenotypes related to addiction, restless leg syndrome, neurofibrillary pathology in Alzheimer's disease, cognitive impairment/intellectual disability, mood lability, and obsessive-compulsive disorder. We review PTPRD's discovery, gene fami ...[more]

PMID: 30648269

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PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes.

Publications

PTPRD: neurobiology, genetics, and initial pharmacology of a pleiotropic contributor to brain phenotypes.

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