Alzheimer's disease: Key developments support promising perspectives for therapy.
Pharmacol Res
; 146: 104316, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31260730
ABSTRACT
Alzheimer's is the neurodegenerative disease affecting the largest number of patients in the world. In spite of the intense research of the last decades, progress about its knowledge and therapy was limited. In particular, various cytotoxic processes remained debated, while the few drugs approved for therapy were of only marginal relevance. Recent studies have identified key aspects of the disease, such as the mechanisms governing the development of pathology. In order to operate the Aß peptide, known as the key factor, requires a complex assembled by its high affinity binding to PrPc, a cell surface prion protein, and mGluR5, a metabotropic glutamate receptor. Aß and its associates bind also phosphorylated tau transferred to the extracellular space, with final activation of intracellular cytotoxic signals. Pathology is further affected by factors (including genes, receptors and their agonists) and by glial cells governing (via vesicles, cytokines and enzymes) cell immunology, inflammation and oxidative stress. Concomitant to pathology studies, strong attempts have been made for the development of new, effective therapies. Critical for this are biomarkers, by which Alzheimer's patients are recognized even before appearance of their symptoms. The question was whether patients take advantage from drugs not yet approved. The latter, first identified in mice, were found effective also in men, however only before appearance or at early stage of the disease. In other words, the drugs not yet approved induce effective protection of patients still healthy or in a preliminary stage of the disease. In contrast, developed Alzheimer's disease is practically irreversible.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Pharmacol Res
Ano de publicação:
2019
Tipo de documento:
Article