γ-Secretase Pharmacology: What Pharmacology Will Work for Alzheimer's Disease?

γ-Secretase Pharmacology: What Pharmacology Will Work for Alzheimer's Disease?

1 Neuroscience Biology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA 2 TopiVert Pharma Ltd., Imperial College Incubator, Bessemer Building Level 1, Imperial College, London SW7 2AZ, UK 3Neural Pathways Discovery, GlaxoSmithKline, Singapore Research Center, Singapore 138667 4Department of Neuropathology and Neuroscience, Graduate School of Pharmac...

Pharmacology – Prep Manual for Undergraduates

Identification and Preclinical Pharmacology of the γ-Secretase Modulator BMS-869780

Alzheimer's disease is the most prevalent cause of dementia and is associated with accumulation of amyloid-β peptide (Aβ), particularly the 42-amino acid Aβ1-42, in the brain. Aβ1-42 levels can be decreased by γ-secretase modulators (GSM), which are small molecules that modulate γ-secretase, an enzyme essential for Aβ production. BMS-869780 is a potent GSM that decreased Aβ1-42 and Aβ1-40 and i...

Robust Translation of γ-Secretase Modulator Pharmacology across Preclinical Species and Human Subjects

The amyloid-β peptide (Aβ)-in particular, the 42-amino acid form, Aβ1-42-is thought to play a key role in the pathogenesis of Alzheimer's disease (AD). Thus, several therapeutic modalities aiming to inhibit Aβ synthesis or increase the clearance of Aβ have entered clinical trials, including γ-secretase inhibitors, anti-Aβ antibodies, and amyloid-β precursor protein cleaving enzyme inhibitors. A...

pharmacology – prep manual for undergraduates

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