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Alvos TerapĂȘuticos na Doença de Alzheimer
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A DA (Doença de Alzheimer) foi descoberta em 1906 por Alois Alzheimer. Representa a forma mais comum de demĂȘncia com uma prevalĂȘncia de 1-2% aos 65 anos que aumenta para cerca de 35% aos 85. Em Portugal estima-se que existam 90.000 pessoas com DA. Define-se como um distĂșrbio neurodegenerativo, progressivo e irreversĂvel, de aparecimento insidioso que acarreta perda de memĂłria e diversos distĂșrbios cognitivos; Ă© caracterizada por perda sinĂĄptica e neuronal progressiva e pelo diagnĂłstico de placas senis ÎČA (pĂ©ptido ÎČ-amilĂłide) e ENFs (emaranhados neurofibrilhares) de proteĂna tau, activação da glia e inflamação.
Os alvos terapĂȘuticos da DA tĂȘm evoluĂdo lentamente, apesar dos marcados avanços cientĂficos das Ășltimas dĂ©cadas. Actualmente os Ășnicos fĂĄrmacos aprovados em Portugal pertencem Ă classe dos IAChE (inibidores da acetilcolinesterase) e inibidores NMDA (receptor N-metil-D-aspartato). Estes compostos tĂȘm a desvantagem de actuarem na sintomatologia nĂŁo intervindo na progressĂŁo da doença. Assim, tornou-se evidente a necessidade da investigação de molĂ©culas modificadoras da DA, que actuem especificamente nos mecanismos fisiopatolĂłgicos chave, como a cascata ÎČ-amilĂłide, proteĂna tau ou neuroinflamação.
Apesar de racionalmente correcto, o paradigma Single Target nĂŁo tem sido suficiente devido Ă complexa rede fisiopatolĂłgica que estĂĄ na base da DA. Portanto, o conceito de ligando Multi Target surge como perspectiva futura mais proeminente de terapĂȘutica. VĂĄrios investigadores tĂȘm centrado a sua investigação nesta premissa, destacando-se B. H. Youdim com os compostos Ladostigil, M30, M30D, Nitromemantina, EGCG (do InglĂȘs, Epigallocatechin-3-gallate) e Resveratrol.
AD (Alzheimerâs Disease) was discovered in 1906 by Alois Alzheimer. The disease represents the most common form of dementia with a prevalence of 1-2% at the age of 65 which increases to about 35% at 85. In Portugal it is estimated that there are 90.000 persons suffering from AD. Defined as a neurodegenerative, progressive and irreversible illness it has an insidious onset that leads to memory loss and several cognitive disturbances; it is characterized by gradual neuronal and synaptic loss, the diagnostic of AÎČ senile plaques and NFTs of tau protein, glial activation and inflammation. Despite the noticeable scientific advances of recent decades the therapeutic targets of AD have evolved slowly. Presently the only approved drugs in Portugal belong to the class of AChEIs and NMDA inhibitors. These compounds have the disadvantage of acting only on the symptoms not interfering in the progression of the disease. Thus it became evident the need to research molecules capable of modifying AD that act specifically on the key pathophysiological mechanisms such as amyloid-ÎČ cascade, tau protein or neuroinflammation. While rationally correct the Single Target paradigm has not been sufficient due to the complex pathophysiological network that underpins AD. Therefore, the concept of Multiple Target ligand appears as the most prominent future perspective of therapeutic. Several researchers have focused their research on this premise standing out B. H. Youdim with Ladostigil, M30, M30D, Nitromemantine, EGCG and Resveratrol compounds.
AD (Alzheimerâs Disease) was discovered in 1906 by Alois Alzheimer. The disease represents the most common form of dementia with a prevalence of 1-2% at the age of 65 which increases to about 35% at 85. In Portugal it is estimated that there are 90.000 persons suffering from AD. Defined as a neurodegenerative, progressive and irreversible illness it has an insidious onset that leads to memory loss and several cognitive disturbances; it is characterized by gradual neuronal and synaptic loss, the diagnostic of AÎČ senile plaques and NFTs of tau protein, glial activation and inflammation. Despite the noticeable scientific advances of recent decades the therapeutic targets of AD have evolved slowly. Presently the only approved drugs in Portugal belong to the class of AChEIs and NMDA inhibitors. These compounds have the disadvantage of acting only on the symptoms not interfering in the progression of the disease. Thus it became evident the need to research molecules capable of modifying AD that act specifically on the key pathophysiological mechanisms such as amyloid-ÎČ cascade, tau protein or neuroinflammation. While rationally correct the Single Target paradigm has not been sufficient due to the complex pathophysiological network that underpins AD. Therefore, the concept of Multiple Target ligand appears as the most prominent future perspective of therapeutic. Several researchers have focused their research on this premise standing out B. H. Youdim with Ladostigil, M30, M30D, Nitromemantine, EGCG and Resveratrol compounds.
Descrição
Trabalho Final de Mestrado Integrado, CiĂȘncias FarmacĂȘuticas, Universidade de Lisboa, Faculdade de FarmĂĄcia, 2014
Palavras-chave
Doença de Alzheimer ÎČ-amilĂłide ProteĂna tau Neuroinflamação Multi Target Mestrado Integrado - 2014