scholarly journals Neurodegeneration in Alzheimer Disease: Role of Amyloid Precursor Protein and Presenilin 1 Intracellular Signaling

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Mario Nizzari ◽  
Stefano Thellung ◽  
Alessandro Corsaro ◽  
Valentina Villa ◽  
Aldo Pagano ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Precursor Protein ◽  
Presenilin 1 ◽  
Recent Theory ◽  
Intracellular Signals ◽  
Transduction Mechanisms

Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.

scholarly journals Molecular Mechanisms of Alzheimer Disease Protection by the A673T Allele of Amyloid Precursor Protein

2014 ◽  
Vol 289 (45) ◽  
pp. 30990-31000 ◽  
Author(s):  
Janice A. Maloney ◽  
Travis Bainbridge ◽  
Amy Gustafson ◽  
Shuo Zhang ◽  
Roxanne Kyauk ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Molecular Mechanisms ◽  
Precursor Protein

G-lymphatic, vascular and immune pathways for Aβ clearance cascade and therapeutic targets for Alzheimer’s disease

2020 ◽  
Vol 23 ◽  
Author(s):  
Saurav Chakraborty ◽  
Jyothsna ThimmaReddygari ◽  
Divakar Selvaraj
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Complement System ◽  
Therapeutic Targets ◽  
Neuronal Cell ◽  
Precursor Protein ◽  
Amyloid Beta Peptide ◽  
Beta Peptide ◽  
Immune Pathways

The Alzheimer disease is a age related neurodegenerative disease. The factors causing alzheimer disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer disease progression. Among them, neuroinflammation, oxidative stress and apoptosis play a major role because of accumulation of extracellular amyloid beta peptides. Here, the clearance of amyloid beta peptide plays a major role because of the imbalance in the production and clearance of the amyloid beta peptide. Additionally, neuroinflammation by microglia, astrocytes, cytokines, chemokines and the complement system also have a major role in Alzheimer disease. The physiological clearance pathways involved in amyloid beta peptide are glymphatic, vascular and immune pathways. Amyloid precursor protein, low density lipoprotein receptor-related protein 1, receptor for advanced glycation end product, apolipoprotein E, clusterin, aquaporin 4, auto-antibodies, complement system, cytokines and microglia are involved in amyloid beta peptide clearance pathways across the blood brain barrier. The plaque formation in the brain by alternative splicing of amyloid precursor protein and production of misfolded protein results in amyloid beta agglomeration. This insoluble amyloid beta leads to neurodegenerative cascade and neuronal cell death occurs. Studies had shown disturbed sleep may be a risk factor for dementia and cognitive decline. In this review, the therapeutic targets for alzheimer disease via focussing on pathways for amyloid beta clearance are discussed.

scholarly journals Amyloid Precursor Protein in Platelets of Patients With Alzheimer Disease

2001 ◽  
Vol 58 (3) ◽  
Author(s):  
Barbara Borroni ◽  
Francesca Colciaghi ◽  
Lucia Pastorino ◽  
Carla Pettenati ◽  
Elisabetta Cottini ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Precursor Protein

scholarly journals The Role of Presenilin-1 in the γ-Secretase Cleavage of the Amyloid Precursor Protein of Alzheimer's Disease

2000 ◽  
Vol 275 (3) ◽  
pp. 1525-1528 ◽  
Author(s):  
Jean-Noël Octave ◽  
Rachid Essalmani ◽  
Bernadette Tasiaux ◽  
Jean Menager ◽  
Christian Czech ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Presenilin 1

AMYLOID PRECURSOR PROTEIN IN SENILE PLAQUES OF ALZHEIMER DISEASE

The Lancet ◽  
1988 ◽  
Vol 332 (8613) ◽  
pp. 746 ◽  
Author(s):  
George Perry ◽  
Sandra Lipphardt ◽  
Madhu Kancherla ◽  
Pierluigi Gambetti ◽  
Linda Maggiora ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Senile Plaques ◽  
Precursor Protein

scholarly journals P3-385: Presenilin 1 is involved in the maturation of beta-site amyloid precursor protein-cleaving enzyme 1(BACE1)

2006 ◽  
Vol 2 ◽  
pp. S489-S489
Author(s):  
Akira Kuzuya ◽  
Kengo Uemura ◽  
Ayae Kinoshita ◽  
Shun Shimohama
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Presenilin 1

scholarly journals The Amyloid Precursor Protein Intracellular Domain-Fe65 Multiprotein Complexes: A Challenge to the Amyloid Hypothesis for Alzheimer's Disease?

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Daniel A. Bórquez ◽  
Christian González-Billault
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Molecular Mechanisms ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Intracellular Domain ◽  
Multiprotein Complexes ◽  
Amyloid Cascade

Since its proposal in 1994, the amyloid cascade hypothesis has prevailed as the mainstream research subject on the molecular mechanisms leading to the Alzheimer's disease (AD). Most of the field had been historically based on the role of the different forms of aggregation ofβ-amyloid peptide (Aβ). However, a soluble intracellular fragment termed amyloid precursor protein (APP) intracellular domain (AICD) is produced in conjunction with Aβfragments. This peptide had been shown to be highly toxic in both culture neurons and transgenic mice models. With the advent of this new toxic fragment, the centerpiece for the ethiology of the disease may be changed. This paper discusses the potential role of multiprotein complexes between the AICD and its adapter protein Fe65 and how this could be a potentially important new agent in the neurodegeneration observed in the AD.

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