To investigate the spectrum and mechanism of Ngb's neuroprotective action, we studied the effect of transgenic overexpression of Ngb on NMDA and beta-amyloid (Abeta) toxicity in murine cortical neuron cultures in vitro and on the phenotype of Alzheimer's disease (AD) transgenic (APP(Sw,Ind)) mice.
Neurons from mutant hiPSC lines express PSEN1-A246E mutations themselves and show AD-like biochemical features, that is, amyloidogenic processing of amyloid precursor protein (APP) indicated by an increase in β-amyloid (Aβ)42/Aβ40 ratio.
Thus it is generally believed that the aberrant processing of APP leads to increased beta-amyloid secretion that in turn leads to subsequent plaque formation and Alzheimer's disease.
This review will focus on the contributions that studies of APP processing have brought to the understanding of a novel nuclear signalling pathway that may contribute to the pathology of AD and may provide new therapeutic opportunities.
Aberrant cleavage of amyloid precursor protein and accumulation of Aβ in the form of the plaque or neurofibrillary tangles are the known primary culprits of AD pathogenesis and target for various regulatory mechanisms.
These new mechanistic insights into the role of triplication of genes on chromosome 21, other than APP, in the development of Alzheimer's disease in individuals who have Down syndrome may have implications for the treatment of this common cause of neurodegeneration.
As a result, the nanochaperone reduces Aβ burden, attenuates Aβ-induced inflammation, and eventually rescues the cognitive deficits of APP/PS1 transgenic AD mice.
A better understanding of the role of APP processing and folate and homocysteine in neuronal homeostasis throughout life consist revealing novel and relatively inexpensive approaches for preventing and treating AD.
We previously reported that PGC-1α also regulates the transcription of β-APP cleaving enzyme (BACE1), the main enzyme involved in Aβ generation, and its expression is decreased in AD patients.
Pathological amino-acid substitutions in the amyloid precursor protein (APP) and chemical γ-secretase modulators affect the processing of APP by the γ-secretase complex and the production of the amyloid-beta peptide Aβ42, the accumulation of which is considered causative of Alzheimer's disease.
Fibrillar beta-amyloid peptide, a major component of senile plaques in AD brain, is known to induce microglial-mediated neurotoxicity under certain conditions, but some recent studies support the notion that Abeta oligomers are the primary neurotoxins.
APP (amyloid precursor protein) and LRP1 (low-density lipoprotein receptor-related protein 1) have been implicated in the pathogenesis of AD (Alzheimer's disease).
The occurrence of +1 frameshifted proteins, such as amyloid precursor protein (APP+1) and ubiquitin-B (UBB+1) in Down syndrome (DS) has been linked to the onset of Alzheimer's disease (AD).
We recently demonstrated that overexpression of ADAM10 in mice transgenic for human AbetaPP (ADAM10 x APP[V717I]) alleviated functional deficits related to Alzheimer's disease.
Cell-specific effects of ACE polymorphism are suggested, additional studies on neuronal cells might help to understand the role of this polymorphism in AD.
Gender-specific risk for AD has been previously reported, and a biological rationale for involvement of ACE in the AD process is supported by studies exploring the relationship between AD and vascular risk factors such as hypertension.
This study investigated the contribution of type-1 IFN signaling in the neuro-inflammatory response to amyloid-beta (Aβ) in vitro and in the APP/PS1 transgenic mouse model of AD.