p(MGI:Chrm1)

Entity

Name

Chrm1

Namespace

mgi

Namespace Version

20181021

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/f2f993e599694ab5ce989cc39d789a499f75db99/external/mgi-names.belns

This file encodes the article Activation of M1 and M4 muscarinic receptors as potential treatments for Alzheimer’s disease and schizophrenia by Choi et al, 2014

This file encodes the article M1 muscarinic acetylcholine receptor in Alzheimer’s disease by Jiang et al, 2014

In mice with scopolamine-induced deficits, PQCA, a selective M1 mAChR positive allosteric modulator[87], improves not only recognition memory, spatial working memory, and executive function, but also blood-flow in the frontal cortex, though the mechanism is not yet clear. PubMed:24590577

Recently, a novel group of M1 partial agonists was developed (AF102B, AF150(S) and AF267B-i) [129]. In a series of studies using the 3x transgenic-AD mice, which recapitulate the major pathologies of AD [130], chronic AF267B treatment rescued cognitive impairment and decreased Abeta42 and tau pathologies in the cortex and hippocampus. These changes were associated with M1 mAChR-mediated activation of the TNFalpha-converting enzyme ADAM17/TACE, decreased BACE1 steady state levels and inhibition of GSK3beta [130]. PubMed:18986241

Finally, studies in mice exhibiting AD-like Abeta plaque pathologies found that deletion of M1 increased amyloidogenic processes, suggesting that M1 may play a role in regulating AD disease progression.51 PubMed:24511233

Among the mAChR family members, the M1 subtype makes up 50–60% of the total and is predominantly expressed in all major areas of the forebrain, including the hippocampus, cerebral cortex, corpus striatum, and thalamus[36-38]. M1 mAChR-knockout mice show a series of cognitive defi cits and impairments in long-term potentiation, indicating that the M1 subtype is physiologically linked to multiple functions such as synaptic plasticity, neuronal excitability, neuronal differentiation during early development, and learning and memory PubMed:24590577

Among the mAChR family members, the M1 subtype makes up 50–60% of the total and is predominantly expressed in all major areas of the forebrain, including the hippocampus, cerebral cortex, corpus striatum, and thalamus[36-38]. M1 mAChR-knockout mice show a series of cognitive defi cits and impairments in long-term potentiation, indicating that the M1 subtype is physiologically linked to multiple functions such as synaptic plasticity, neuronal excitability, neuronal differentiation during early development, and learning and memory PubMed:24590577

though there are contradictory findings showing that the alpha-secretase-mediated APP processing via M1 mAChR stimulation is not modulated by the ERK1/MEK cascade[71]. On the other hand, loss of M1 mAChR increases amyloidogenic APP processing in neurons and promotes brain Abeta plaque pathology in a mouse model of AD PubMed:24590577

though there are contradictory findings showing that the alpha-secretase-mediated APP processing via M1 mAChR stimulation is not modulated by the ERK1/MEK cascade[71]. On the other hand, loss of M1 mAChR increases amyloidogenic APP processing in neurons and promotes brain Abeta plaque pathology in a mouse model of AD PubMed:24590577

Recently, a novel group of M1 partial agonists was developed (AF102B, AF150(S) and AF267B-i) [129]. In a series of studies using the 3x transgenic-AD mice, which recapitulate the major pathologies of AD [130], chronic AF267B treatment rescued cognitive impairment and decreased Abeta42 and tau pathologies in the cortex and hippocampus. These changes were associated with M1 mAChR-mediated activation of the TNFalpha-converting enzyme ADAM17/TACE, decreased BACE1 steady state levels and inhibition of GSK3beta [130]. PubMed:18986241