Thenumber of Alzheimer’s Disease (AD) patients is considerably mounting in
association with prolongation of life span and AD is currently a major burden
on society. No beneficial anti-AD drug, however, has been provided as yet. The
most urgent issue, therefore, is to develop drugs for AD.
Wehave found that cis-unsaturated free fatty acids such as arachidonic, linoleic
and linolenic acid, persistently facilitates hippocampal synaptic transmission
by targeting presynaptic nicotinic ACh receptor under the control of PKC. Cis-unsaturated
free fatty acids, however, are promptly metabolized and decomposed before
arriving in the brain, even though the fatty acids are orally or intravenously
taken into the body. To resolve this problem, we have synthesized a variety of
derivatives of cis-unsaturated free fatty acids, that exhibit stable
bioactivities, and obtained the most effective compound a linoleic acid
derivative with cyclopropane rings instead of cis-double bonds.
Beneficialanti-AD drugs require protection of neuronal apoptosis and facilitation of synaptic
transmission relevant to cognitive functions. I show here that DCP-LA has the
actions of both anti-apoptosis and cognitive enhancement. Tau, which is
abundantly expressed in neurons of the central nervous system, stabilizes
microtubules by interacting with tubulin. When phosphorylated excessively, Tau
becomes a trigger for tauopathies. Tauopathies are a class of neurodegenerative
diseases associated with aggregation of hyperphosphorylated Tau in an insoluble
form in the brain, referred to as Neurofibrillary Tangles (NFT), which include
AD, frontotemporal dementia and parkinsonism linked to chromosome 17,
progressive supranuclear palsy, Pick’s disease, and corticobasal degeneration.
AD is a really tragic disease in which a human being loses human dignity. AD is
characterized by extensive deposition of amyloid β (A β) and formation of NFT.
To date, none of Aβ-directed drugs for AD.
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