Tratamento farmacológico da doença de Alzheimer: situação atual e perspectivas futuras.

Abstract

Worldwide, population goes by a fast aging process. This has caused, among other implications, a significant increase on the prevalence of chronic-degenerative, among them, the dementias. The Alzheimer Disease (AD) is the most common form of dementia and has earned notoriety by its huge socioeconomic impact. Despite all efforts from the scientific community, until the present moment, there is no cure for the AD, neither approved treatments that prevent the symptoms progression. The pharmacons approved up to now for this infirmity - donepezil, rivastigmine, galantamine, and memantine - are limited to the delay of its evolution, giving only a partial and temporary improvement to the individual functional status. The objective of this work was review the actual pharmacological treatment of the AD and the future pharmacons in investigation. The most studied strategy has been blocking the proteolytic machinery, which produces the substance βA. The inhibition of β e γ-secretase pathways and the α-secretase pathway stimulation has been the most promising strategies. Another quite promising strategy is the inhibition of tau protein hyperphosphorylation, which searches the NFTs reduction. Recent studies, using cellular models, demonstrated that certain substances are capable of preclude the tau protein aggregation and even dissolve the already formed aggregates. New cholinergics in investigation include allosteric agonists from the muscarinic acetylcholine receptors and also agonists from certain subtypes of nicotinic receptors. Once the mythocondrial dysfunction and oxidative stress can perform a role on the DA development, there has been proposed much effort to demonstrate the therapeutic potential of antioxidants in the treatment of this disease. The natural active ingredients exploration from medicinal plants for the treatment of AD has attracted the substantial attention on the last years being target of many researches. Other therapeutic strategies in development include the use of nerve growth factor, phosphodiesterase-5 inhibitors, inhibition of receptor for advanced glycation end products, among others.