Alzheimer's disease (AD) Alzheimer's disease (AD) has become a major world-wide health problem with ever rising costs associated with the treatment and care of afflicted individuals. As life expectancy has increased the occurrence of dementia has also increased. Hypertension during middle adulthood is correlated with a significantly elevated risk of cognitive impairment later in life. Treatment with antihypertensive drugs, particularly angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), has been reported to reduce the likelihood and slow the progression of AD.
Angiotensin IV (AngIV: VYIHPF) related peptides have long been recognized as procognitive agents with potential as antidementia therapeutics. A previous study demonstrated that the core structural information required to impart the procognitive activity of. Chemical modifications of the AngIV analog, norleucine-angiotensin IV, resides in its three N-terminal amino acids, Nle-Tyr-Ile, which were designed to increase hydrophobicity and decrease hydrogen bonding, yielded an orally active, blood-barrier permeant, metabolically stabilized analog, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (dihexa), that exhibits excellent antidementia activity in the rat models and suggested that dihexa may have therapeutic potential as a treatment of disorders, such as Alzheimer's disease. More information see Dr Harding JW laboratory website.
References:
McCoy AT, et al. (2013) Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents. J Pharmacol Exp Ther. 344:141-154.
Kawas LH, et al. (2011) Mimics of the dimerization domain of hepatocyte growth factor exhibit anti-Met and anticancer activity. J Pharmacol Exp Ther. 339:509-518.
Wright JW and Harding JW (2010) The brain RAS and Alzheimer's disease. Exp Neurol. 223(2):326-33.