P3-157: A novel microRNA interaction relevant to alzheimer's disease pathogenesis and drug target discovery: miR-346 induces expression of amyloid precursor protein

2011 ◽  
Vol 7 ◽  
pp. S566-S567 ◽  
Author(s):  
Justin Long ◽  
Debomoy Lahiri
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Drug Target ◽  
Precursor Protein ◽  
Disease Pathogenesis ◽  
Drug Target Discovery ◽  
Target Discovery

Memapsin 2, a drug target for Alzheimer's disease

2003 ◽  
Vol 70 ◽  
pp. 213-220 ◽  
Author(s):  
Gerald Koelsch ◽  
Robert T. Turner ◽  
Lin Hong ◽  
Arun K. Ghosh ◽  
Jordan Tang
Keyword(s):  
Crystal Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition State ◽  
Amyloid Precursor Protein ◽  
Therapeutic Target ◽  
Drug Target ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Memapsin 2

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.

A Map of Alzheimer’s Disease–Signaling Pathways: A Hope for Drug Target Discovery

2013 ◽  
Vol 93 (5) ◽  
pp. 399-401 ◽  
Author(s):  
S Ogishima ◽  
S Mizuno ◽  
M Kikuchi ◽  
A Miyashita ◽  
R Kuwano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathways ◽  
Drug Target ◽  
Drug Target Discovery ◽  
Target Discovery

scholarly journals Mutations of beta-amyloid precursor protein alter the consequence of Alzheimer’s disease pathogenesis

2019 ◽  
Vol 14 (4) ◽  
pp. 658 ◽  
Author(s):  
Hong Qing ◽  
Nuo-Min Li ◽  
Ke-Fu Liu ◽  
Yun-Jie Qiu ◽  
Huan-Huan Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Beta Amyloid ◽  
Precursor Protein ◽  
Disease Pathogenesis

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: 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.

scholarly journals A clinical dose of angiotensin-converting enzyme (ACE) inhibitor and heterozygous ACE deletion exacerbate Alzheimer's disease pathology in mice

2019 ◽  
Vol 294 (25) ◽  
pp. 9760-9770 ◽  
Author(s):  
Shuyu Liu ◽  
Fujiko Ando ◽  
Yu Fujita ◽  
Junjun Liu ◽  
Tomoji Maeda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Amyloid Precursor Protein ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Precursor Protein ◽  
Causative Role ◽  
Converting Enzyme ◽  
Clinical Dose

Inhibition of angiotensin-converting enzyme (ACE) is a strategy used worldwide for managing hypertension. In addition to converting angiotensin I to angiotensin II, ACE also converts neurotoxic β-amyloid protein 42 (Aβ42) to Aβ40. Because of its neurotoxicity, Aβ42 is believed to play a causative role in the development of Alzheimer's disease (AD), whereas Aβ40 has neuroprotective effects against Aβ42 aggregation and also against metal-induced oxidative damage. Whether ACE inhibition enhances Aβ42 aggregation or impairs human cognitive ability are very important issues for preventing AD onset and for optimal hypertension management. In an 8-year longitudinal study, we found here that the mean intelligence quotient of male, but not female, hypertensive patients taking ACE inhibitors declined more rapidly than that of others taking no ACE inhibitors. Moreover, the sera of all AD patients exhibited a decrease in Aβ42-to-Aβ40–converting activity compared with sera from age-matched healthy individuals. Using human amyloid precursor protein transgenic mice, we found that a clinical dose of an ACE inhibitor was sufficient to increase brain amyloid deposition. We also generated human amyloid precursor protein/ACE+/− mice and found that a decrease in ACE levels promoted Aβ42 deposition and increased the number of apoptotic neurons. These results suggest that inhibition of ACE activity is a risk factor for impaired human cognition and for triggering AD onset.

The Interaction Between Contactin and Amyloid Precursor Protein and Its Role in Alzheimer’s Disease

Neuroscience ◽  
2020 ◽  
Vol 424 ◽  
pp. 184-202
Author(s):  
Rosemary A. Bamford ◽  
Jocelyn Widagdo ◽  
Natsuki Takamura ◽  
Madeline Eve ◽  
Victor Anggono ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Precursor Protein
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