Design and Synthesis of β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1) Inhibitors with in Vivo Brain Reduction of β-Amyloid Peptides

2012 ◽  
Vol 55 (21) ◽  
pp. 9346-9361 ◽  
Author(s):  
Britt-Marie Swahn ◽  
Karin Kolmodin ◽  
Sofia Karlström ◽  
Stefan von Berg ◽  
Peter Söderman ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Amyloid Peptides ◽  
Design And Synthesis ◽  
Β Amyloid

scholarly journals Neuronal aging potentiates beta-amyloid generation via amyloid precursor protein endocytosis

2019 ◽  
Author(s):  
Tatiana Burrinha ◽  
Ricardo Gomes ◽  
Ana Paula Terrasso ◽  
Cláudia Guimas Almeida
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
App Processing ◽  
Early Endosomes ◽  
Primary Mouse ◽  
Β Amyloid ◽  
Aβ Production

AbstractAging increases the risk of Alzheimer’s disease (AD). During normal aging synapses decline and β-Amyloid (Aβ) accumulates. An Aβ defective clearance with aging is postulated as responsible for Aβ accumulation, although a role for increased Aβ production with aging can also lead to Aβ accumulation. To test this hypothesis, we established a long-term culture of primary mouse neurons that mimics neuronal aging (lysosomal lipofuscin accumulation and synapse decline). Intracellular endogenous Aβ42 accumulated in aged neurites due to increased amyloid-precursor protein (APP) processing. We show that APP processing is up-regulated by a specific age-dependent increase in APP endocytosis. Endocytosed APP accumulated in early endosomes that, in turn were found augmented in aged neurites. APP processing and early endosomes up-regulation was recapitulated in vivo. Finally, we found that inhibition of Aβ production reduced the decline in synapses in aged neurons. We propose that potentiation of APP endocytosis by neuronal aging increases Aβ production, which contributes to aging-dependent decline in synapses.SummaryHow aging increases the risk of Alzheimer’s disease is not clear. We show that normal neuronal aging increases the intracellular production of β-amyloid, due to an upregulation of the amyloid precursor protein endocytosis. Importantly, increased Aβ production contributes to the aging-dependent synapse loss.

Nerve growth factor does not influence the expression of β amyloid precursor protein mRNA in rat brain: in vivo and in vitro studies

1993 ◽  
Vol 620 (2) ◽  
pp. 292-296 ◽  
Author(s):  
Gianluigi Forloni ◽  
Roberto Del Bo ◽  
Nadia Angeretti ◽  
Simona Smiroldo ◽  
Nadia Gabellini ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Amyloid Precursor Protein ◽  
Rat Brain ◽  
Precursor Protein ◽  
In Vitro Studies ◽  
Nerve Growth ◽  
Β Amyloid

Block of LTP in rat hippocampus in vivo by β-amyloid precursor protein fragments

Neuroreport ◽  
1997 ◽  
Vol 8 (15) ◽  
pp. 3213-3217 ◽  
Author(s):  
William K. Cullen ◽  
Yoo-Hun Suh ◽  
Roger Anwyl ◽  
Michael J. Rowan
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Rat Hippocampus ◽  
Protein Fragments ◽  
Β Amyloid

scholarly journals Increased Generation of Alternatively Cleaved β-Amyloid Peptides in Cells Expressing Mutants of the Amyloid Precursor Protein Defective in Endocytosis

2000 ◽  
Vol 74 (3) ◽  
pp. 1131-1139 ◽  
Author(s):  
Renzo Cescato ◽  
Eric Dumermuth ◽  
Martin Spiess ◽  
Paolo A. Paganetti
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Amyloid Peptides ◽  
Β Amyloid ◽  
In Cells

NGF deprivation and neuronal degeneration trigger altered β-amyloid precursor protein gene expression in the rat superior cervical ganglia in vivo and in vitro

1993 ◽  
Vol 17 (3-4) ◽  
pp. 328-334 ◽  
Author(s):  
Carthage J. Smith ◽  
Eugene M. Johnson ◽  
Patricia Osborne ◽  
Robert S. Freeman ◽  
Isabelle Neveu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amyloid Precursor Protein ◽  
Protein Gene ◽  
Neuronal Degeneration ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Gene ◽  
Β Amyloid ◽  
Cervical Ganglia

β amyloid precursor protein metabolism is regulated in vivo by protein kinase C in rat brain

1995 ◽  
Vol 31 ◽  
pp. 123
Author(s):  
A. Caputi ◽  
J. Buxbaum ◽  
M. Cimino ◽  
L. Pastorino ◽  
F. Cattabeni ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Amyloid Precursor Protein ◽  
Rat Brain ◽  
Protein Metabolism ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Metabolism ◽  
Kinase C ◽  
Β Amyloid

Effects of altered RTN3 expression on BACE1 activity and Alzheimer’s neuritic plaques

2017 ◽  
Vol 28 (2) ◽  
pp. 145-154 ◽  
Author(s):  
Md Golam Sharoar ◽  
Riqiang Yan
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Neuritic Plaques ◽  
Amyloid Peptides ◽  
Protein Levels ◽  
Bace1 Expression ◽  
Β Amyloid ◽  
Tubular Endoplasmic Reticulum ◽  
Bace1 Activity

AbstractReticulon 3 (RTN3), which is a member of the reticulon family of proteins, has a biochemical function of shaping tubular endoplasmic reticulum. RTN3 has also been found to interact with β-site amyloid precursor protein cleaving enzyme 1 (BACE1), which initiates the generation of β-amyloid peptides (Aβ) from amyloid precursor protein. Aβ is the major proteinaceous component in neuritic plaques, which constitute one of the major pathological features in brains of Alzheimer’s disease (AD) patients. Mice deficient in or overexpressing RTN3 have altered amyloid deposition through effects on BACE1 expression and activity. In this review, we will summarize the current findings concerning the role of RTN3 in AD pathogenesis and demonstrate that RTN3 protein levels act as age-dependent modulators of BACE1 activity and Aβ deposition during the pathogenic progression of AD.

Expression of β-Amyloid Precursor Protein Gene Is Developmentally Regulated in Human Muscle Fibers in Vivo and in Vitro

1994 ◽  
Vol 128 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Eva Sarkozi ◽  
Valerie Askanas ◽  
Steven A. Johnson ◽  
Janis McFerrin ◽  
W.King Engel
Keyword(s):  
Amyloid Precursor Protein ◽  
Protein Gene ◽  
Muscle Fibers ◽  
Human Muscle ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Gene ◽  
Developmentally Regulated ◽  
Β Amyloid
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