ABSTRACT
Amyloid plaques and Tau tangles, constitute the pathological hallmarks of the brains of the patients suffering from Alzheimer’s disease. They are identified as far back as 1996 by Alois Alzheimer, a German psychiatrist and neuropathologist, but till this date, how they produce neuronal death remained an enigma. The amyloid cascade theory held its sway until recent times until the emphasis is shifted to the metabolites of amyloid Beta precursor protein (APP). Several metabolites of APP are formed depending on by which pathway, the APP is metabolized, either by the non - amyloidogenic pathway (forming ? - C terminal fragment - CTF? / C83 and the N - terminal fragment sAPP? / P3 and the APP intracellular domain AICD). Or amyloidogenic pathways. ( Forming extracellular A? and APP intracellular domain - AICD). The hyperphosphorylation is held responsible for the tau protein tangles. The over activity of the tau kinases or the failure of inhibition by the tau phosphatases i s implicated, in tau tangle deposits. These biochemical aspects of AD assumed importance in connection with the interventional therapeutic strategies that are developed in the years bygone, as well as those still are in the developing stage. In keeping with this fact, it is attempted to review the essentials of the biochemical aspects of the involved proteins, as related to AD, in this article
ABSTRACT
A doença de Alzheimer (DA) é a forma de demência degenerativa esporádica mais comum. Caracteristicamente ocorre expressiva perda neuronal progressiva em locais específicos nas pessoas atingidas. O distúrbio degenerativo progressivo se caracteriza pela perda de sinapses, de neurônios cerebrais e por depósitos de fibrilas de peptídeos de beta-amilóide extraneuronais, constituindo as placas senis e a presença de agregados intraneuronais da proteína tau, formando os emaranhados neurofibrilares. Fatores genéticos, metabólicos, neuroinflamação, alterações mitocondriais, distúrbios vasculares e processos oxidativos estão envolvidos no desencadear e manutenção de várias doenças neurodegenerativas, incluindo a DA. Todas essas alterações participam no processo fisiopatológico da doença. O objetivo desta revisão é mostrar a associação das várias causas subjacentes ao processo fisiopatológico da DA, com vistas ao desenvolvimento de marcadores biológicos e estratégias terapêuticas.
Alzheimer's disease (AD) is the most common form of sporadic degenerative dementia. Characteristically there is an expressive neuronal loss in specific sites in the affected persons. The progressive degenerative disorder is characterized by synaptic loss, of brain neurons, and by extraneuronal deposition of beta-amyloid fibrils, constituting the senile plaques, and the presence of intraneuronal aggregates of tau protein, forming the neurofibrillary tangles. Genetic factors, metabolic, neuroinflammation, mitochondrial disturbances, vascular disorders and oxidative processes are involved in the onset and maintenance of several neurodegenerative disorders, including AD. All these disturbances participate in the pathophysiological process of the disease. The aim of this review is to show the association of the varied causes underlying the pathophysiological process of AD, having in view the development of biological markers and therapeutic strategies.