bp(HBP:"APP processing")

Entity

Name

APP processing

Namespace

HBP

Namespace Version

20181128

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/7e4be528f12abd28be768b62402fba6e083eaf9e/export/hbp-names.belns

After brucine, several other M1-PAMs have been discovered, including VU0029767, VU0090157, and benzyl quinolone carboxylic acid (BQCA)[115-117]. These compounds do not activate M1 mAChR directly but greatly increase the affi nity of ACh for the M1 subtype. In addition, BQCA is effective in restoring discrimination reversal learning in a mouse model of AD and regulating nonamyloidogenic APP processing[117]. PubMed:24590577

Some studies suggest that M1 mAChR stimulation also leads to activation of ERK1/2, which can modulate alpha-secretase activity and APP processing[67, 73], 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

Another serine protease recently implicated in tau processing is HTRA1. This is a ubiquitously expressed, ATP-independent intracellular protease. Expression is detectable in many tissues, including the nervous system, although expression is low (40).Nonetheless, this enzyme was initially implicated in AD because it may play a role in amyloid processing (41). PubMed:24027553

Another serine protease recently implicated in tau processing is HTRA1. This is a ubiquitously expressed, ATP-independent intracellular protease. Expression is detectable in many tissues, including the nervous system, although expression is low (40).Nonetheless, this enzyme was initially implicated in AD because it may play a role in amyloid processing (41). PubMed:24027553

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

In cultured cells, deregulation of PP2A methylation also affects APP processing (Sontag et al.,2007), neurite outgrowth (Sontag et al.,2010) and tau distribution (Sontag et al.,2013). PubMed:24653673

A multitude of studies have demonstrated that NF-κB directly regulates the transcription and expression of BACE1, thereby eliciting profound effects on AβPP processing and engenderment of Amyloid-β PubMed:28745240

Under physiological conditions activation of NF-κB by endogenous Aβ reduces βAPP, BACE1 and the γ-secretase activity, thereby lowering Aβ processing and facilitating Aβ homeostasis PubMed:25652642

However in AD, exposure to high Aβ concentrations upregulates NF-κB activation increasing βAPP and Aβ processing, precipitating a feed-back loop that favor exacerbated Aβ production PubMed:25652642

Another serine protease recently implicated in tau processing is HTRA1. This is a ubiquitously expressed, ATP-independent intracellular protease. Expression is detectable in many tissues, including the nervous system, although expression is low (40).Nonetheless, this enzyme was initially implicated in AD because it may play a role in amyloid processing (41). PubMed:24027553

Another serine protease recently implicated in tau processing is HTRA1. This is a ubiquitously expressed, ATP-independent intracellular protease. Expression is detectable in many tissues, including the nervous system, although expression is low (40).Nonetheless, this enzyme was initially implicated in AD because it may play a role in amyloid processing (41). PubMed:24027553

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

However in AD, exposure to high Aβ concentrations upregulates NF-κB activation increasing βAPP and Aβ processing, precipitating a feed-back loop that favor exacerbated Aβ production PubMed:25652642