The biological fates of the key initiator of Alzheimer's disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven.
The activity of beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is elevated during aging and in sporadic Alzheimer's disease (AD), but the underlying mechanisms of this change are not well understood. p25/Cyclin-dependent kinase 5 (Cdk5) has been implicated in the pathogenesis of several neurodegenerative diseases, including AD.
We discuss the specific interactions with APP, the capacity to modulate the intracellular itinerary and the proteolytic conversion of APP, a possible involvement in the clearance of Aβ, and the implications of these transmembrane proteins in AD and other neurodegenerative diseases.
Alzheimer's disease (AD) is a neurodegenerative disorder involving the florid deposition of vascular and cerebral plaques composed chiefly of amyloid beta-peptide (A beta) derived from cleavage of the amyloid precursor protein (APP).
Alzheimer's disease (AD) is a neurodegenerative disorder known for the presence of amyloid beta plaques resulting from the sequential action of β-secretase and γ-secretase on amyloid precursor protein.
As spheres of a misfolded protein, betaamy balls resemble both AD Abeta senile plaques and neuronal inclusion bodies associated with other neurodegenerative diseases.
We demonstrate that HARDEN can be applied to the neurodegenerative disease genes C9orf72 and APP, and methylation can be induced via HDR with both single and double stranded methylated repair templates.
In doing so, we aim to invigorate research and discussion around non-amyloidogenic APP processing products and the mechanisms linking mitochondria and complex neurodegenerative disorders such as sporadic Alzheimer's disease.
My findings accounted for epigenetic mechanism in the regulation of alternative APP pre-mRNA splicing as well as for epigenetic control of genomic rearrangements of APP gene may provide therefore new directions not only for investigating the role of APP in neuropathology associated with HGprt-deficiency in LNS and LNVs patients but also for the research in neurodevelopmental and neurodegenerative disorders by which APP gene involved in the pathogenesis of the diseases such as autism, fragile X syndrome (FXS), and Alzheimer's disease (AD) with its diversity and complexity, especially for sporadic form of AD (SAD).
While a commonly accepted model argues that Abeta peptides are the cause of onset and early pathogenesis of Alzheimer's disease, recent discussions challenge this 'Abeta hypothesis' and suggest a direct role for APP in this neurodegenerative disease.
Additional mechanisms have been suggested for the ability of flavonoids to delay the initiation of and/or slow the progression of AD-like pathology and related neurodegenerative disorders, including a potential to inhibit neuronal apoptosis triggered by neurotoxic species (e.g., oxidative stress and neuroinflammation) or disrupt amyloid β aggregation and effects on amyloid precursor protein processing through the inhibition of β-secretase (BACE-1) and/or activation of α-secretase (ADAM10).
Overall, our results suggest strongly that US9 can serve as a molecular driver that targets functional cargos to the APP machinery and can be used as a tool to study the contribution of lipid rafts to neurodegenerative disease conditions where amyloidogenesis has been implicated.
Transgenic Centre for Research in Neurodegenerative Diseases 8 (TgCRND8) mice expressing a double mutant form of human amyloid precursor protein represent a good model of Alzheimer's disease, and can be useful to clarify the involvement of mitogen-activated protein kinases (MAPK) dysregulation in the pathophysiology of this neurodegenerative disorder.
Therefore, inhibition of the IRE-modulated expression of APP and α-Syn or chelation of iron in patient's brains has therapeutic significance to human neurodegenerative diseases.
Together with the demonstration of metal dependent translation of APP mRNA, the involvement of metals in the plaque of AD patients and of increased iron in striatal neurons in the substantia nigra (SN) of Parkinson's disease patients have stimulated the development of metal attenuating agents and iron chelators as a major new therapeutic strategy for the treatment of these neurodegenerative diseases.
This relationship was unexpected given current theories that APP expression occurs as part of a stress response, and suggests that other factors predominate in determining neocortical APP mRNA content in neurodegenerative disorders.