호르몬 그렐린의 수용체는 AD치료 타깃
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그렐린 수용체가 AD 타깃이 될 수 있다는 가능성을 제안하는 논문이 Science Translational Medicine 저널에 2019년 8월 14일자로 게재되었다
Disrupted hippocampal growth hormone secretagogue receptor 1α interaction with dopamine receptor D1 plays a role in Alzheimer′s disease
Abstract
Hippocampal lesions are a defining pathology of Alzheimer’s disease (AD). However, the molecular mechanisms that underlie hippocampal synaptic injury in AD have not been fully elucidated. Current therapeutic efforts for AD treatment are not effective in correcting hippocampal synaptic deficits. Growth hormone secretagogue receptor 1α (GHSR1α) is critical for hippocampal synaptic physiology. Here, we report that GHSR1α interaction with β-amyloid (Aβ) suppresses GHSR1α activation, leading to compromised GHSR1α regulation of dopamine receptor D1 (DRD1) in the hippocampus from patients with AD. The simultaneous application of the selective GHSR1α agonist MK0677 with the selective DRD1 agonist SKF81297 rescued Ghsr1α function from Aβ inhibition, mitigating hippocampal synaptic injury and improving spatial memory in an AD mouse model. Our data reveal a mechanism of hippocampal vulnerability in AD and suggest that a combined activation of GHSR1α and DRD1 may be a promising approach for treating AD.
식욕 조절 호르몬인 그렐린은 해마의 성체신경발생(Adult hippocampal neurogenesis)을 자극해 정상 뇌와 알츠하이머병 뇌의 인지기능을 향상 시킴
Trends in endocrinology & metabolism
Abstract
There is a close relationship between cognition and nutritional status, however, the mechanisms underlying this relationship require elucidation. The stomach hormone, ghrelin, which is released during food restriction, provides a link between circulating energy state and adaptive brain function. The maintenance of such homeostatic systems is essential for an organism to thrive and survive, and accumulating evidence points to ghrelin being key in promoting adult hippocampal neurogenesis and memory. Aberrant neurogenesis is linked to cognitive decline in ageing and neurodegeneration. Therefore, identifying endogenous metabolic factors that regulate new adult-born neurone formation is an important objective in understanding the link between nutritional status and central nervous system (CNS) function. Here, we review current developments in our understanding of ghrelin’s role in regulating neurogenesis and memory function.