Purification and cloning of amyloid precursor protein β-secretase from human brain
A membrane-bound enzyme activity that cleaves full-length APP at the β-secretase cleavage site is described and found to be the predominant β-cleavage activity in human brain, and it is found that human brain β- secretase is a new membrane- bound aspartic proteinase.
Functional gamma‐secretase inhibitors reduce beta‐amyloid peptide levels in brain
These studies represent the first demonstration of a reduction of brain Aβin vivo and will enable a clinical examination of the Aβ hypothesis that Aβ peptide drives the neuropathology observed in Alzheimer's disease.
Ayurvedic medicinal plants for Alzheimer's disease: a review
This review gathers research on various medicinal plants that have shown promise in reversing the Alzheimer's disease pathology and summarizes information concerning the phytochemistry, biological, and cellular activities and clinical applications of these various plants in order to provide sufficient baseline information that could be used in drug discovery campaigns and development process.
Pharmacological Induction of Neuroglobin Expression
Ngb expression was increased by the short-chain fatty acids cinnamic acid and valproic acid, but not by other short- chain fatty acids, histone deacetylase inhibitors, or anticonvulsants, which may have therapeutic potential in the treatment of stroke and other neurological disorders.
Paradoxical effect of TrkA inhibition in Alzheimer's disease models.
The results suggest TrkA inhibition-rather than NGF activation-as a novel therapeutic approach, and raise the possibility that such an approach may counteract the hyperactive signaling resulting from the accumulation of active NGF-TrkA complexes due to reduced retrograde transport.
Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-β peptide and τ levels: target engagement, tolerability and pharmacokinetics in humans
- M. Maccecchini, M. Chang, C. Pan, V. John, H. Zetterberg, N. Greig
- Medicine, BiologyJournal of Neurology Neurosurgery & Psychiatry
- 11 July 2012
Posiphen proved well tolerated and significantly lowered CSF levels of sAPPα, sAPPβ, t-τ, p-τ and specific inflammatory markers, and demonstrated a trend to lower CSF Aβ42, and confirmed that pharmacologically relevant drug/metabolite levels reach brain.
Neuroprotective Sirtuin ratio reversed by ApoE4
- V. Theendakara, Alexander Patent, D. Bredesen
- BiologyProceedings of the National Academy of Sciences
- 21 October 2013
The data support the hypothesis that neuronal connectivity, as reflected in the ratios of critical mediators such as sAPPα:Aβ, SirT1:SirT2, APP:phosphorylated (p)-APP, and Tau:p-Tau, is programmatically altered by ApoE4 and offer a simple system for the identification of program mediators and therapeutic candidates.
Importance of the caspase cleavage site in amyloid-β protein precursor.
The results and implications of studies analyzing the critical nature of the caspase cleavage site of amyloid-β protein precursor for cell death induction, synaptic loss, hippocampal atrophy, long-term potentiation, memory loss, neophobia, and other aspects of the Alzheimer's phenotype are reviewed.
The multi-functional drug tropisetron binds APP and normalizes cognition in a murine Alzheimer's model
Next generation therapeutics for Alzheimer's disease
In searching for new approaches that may succeed where previous ones have failed, it may be instructive to consider the successful therapeutic developments for other chronic illnesses such as cancer and human immunodeficiency virus.