Role of Amyloid Precursor Protein, Amyloid-β and γ-Secretase in Cholesterol Maintenance

2006 ◽  
Vol 3 (4-5) ◽  
pp. 305-311 ◽  
Author(s):  
Tobias Hartmann
2005 ◽  
Vol 33 (5) ◽  
pp. 1116-1118 ◽  
Author(s):  
S.J. Patey ◽  
E.A. Yates ◽  
J.E. Turnbull

The role of HS (heparan sulphate) in the pathology of AD (Alzheimer's disease) is multifaceted. HS and other glycosaminoglycans have been widely reported to be associated with neuritic plaques. HS has also been shown to promote the aggregation of Aβ (amyloid β-peptide), the proteinaceous component of neuritic plaques. Recently, we described a novel and contrasting role for HS in the pathology of AD: HS can inhibit the formation of Aβ, by directly interacting with the protease BACE1 (β-site amyloid precursor protein cleaving enzyme 1; β-secretase 1), that cleaves the amyloid precursor protein and is the rate limiting step in the generation of Aβ. Here, we review the current roles of HS and the potential for HS-derivatives in the treatment of AD.


Biochemistry ◽  
2008 ◽  
Vol 47 (28) ◽  
pp. 7405-7413 ◽  
Author(s):  
Holger Cynis ◽  
Eike Scheel ◽  
Takaomi C. Saido ◽  
Stephan Schilling ◽  
Hans-Ulrich Demuth

2009 ◽  
Vol 284 (18) ◽  
pp. 11863-11872 ◽  
Author(s):  
Madepalli K. Lakshmana ◽  
Il-Sang Yoon ◽  
Eunice Chen ◽  
Elizabetta Bianchi ◽  
Edward H. Koo ◽  
...  

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.


2000 ◽  
Vol 275 (3) ◽  
pp. 1525-1528 ◽  
Author(s):  
Jean-Noël Octave ◽  
Rachid Essalmani ◽  
Bernadette Tasiaux ◽  
Jean Menager ◽  
Christian Czech ◽  
...  

2019 ◽  
Vol 141 (3) ◽  
Author(s):  
I. A. Kuznetsov ◽  
A. V. Kuznetsov

Modeling of intracellular processes occurring during the development of Alzheimer's disease (AD) can be instrumental in understanding the disease and can potentially contribute to finding treatments for the disease. The model of intracellular processes in AD, which we previously developed, contains a large number of parameters. To distinguish between more important and less important parameters, we performed a local sensitivity analysis of this model around the values of parameters that give the best fit with published experimental results. We show that the influence of model parameters on the total concentrations of amyloid precursor protein (APP) and tubulin-associated unit (tau) protein in the axon is reciprocal to the influence of the same parameters on the average velocities of the same proteins during their transport in the axon. The results of our analysis also suggest that in the beginning of AD the aggregation of amyloid-β and misfolded tau protein have little effect on transport of APP and tau in the axon, which suggests that early damage in AD may be reversible.


PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135741 ◽  
Author(s):  
Isabelle Bourdet ◽  
Aurélie Lampin-Saint-Amaux ◽  
Thomas Preat ◽  
Valérie Goguel

2010 ◽  
Vol 4 (2) ◽  
pp. 268-272 ◽  
Author(s):  
Naouel Ben Khalifa ◽  
Joanne Van Hees ◽  
Bernadette Tasiaux ◽  
Sandra Huysseune ◽  
Steven O. Smith ◽  
...  

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