Alzheimer s disease (AD) is a complex multifactorial syndrome unlikely to arise from a single causal factor, but due to a number of different but related biological alterations that contribute to its pathogenesis. None of the presently marketed drugs, although valuable in improving cognitive, behavioral, and functional impairments, alter AD progression, and the goal of an effective disease-modifying treatment is still unmet. Nowadays, mechanism-based drug-design approaches are mainly directed toward two proteins, amyloid b (Ab) and tau. Ab is the core constituent of senile plaques, one of the key pathological characteristics of AD, whereas phosphorylated tau is the main component of neurofibrillary tangles, the other hallmark lesion of AD. Despite enormous research effort, no new molecules that interfere with the biochemical pathways of either Ab or tau have been approved so far for the treatment of AD. This failure is probably due to the weakness of the classic drug discovery approach based on the “one molecule, one target” paradigm, which might prove inadequate when the molecular complexity of the disease is addressed. In fact, the multifactorial nature of AD and the current lack of an accepted unitary theory to account for AD neurodegeneration have formed the basis of a growing consensus that single compounds are required that are able to interact with several molecular targets in the neurotoxic cascade (the innovative “one molecule, multiple targets” paradigm). Herein, we report on a new drug candidate (memoquin, patent pending) derived from a program aimed at creating multifunctional molecules to interfere with different key target points of AD neurodegeneration.

A small molecule targeting the multifactorial nature of Alzheimer's disease

CAVALLI, ANDREA;BOLOGNESI, MARIA LAURA;ANDRISANO, VINCENZA;BARTOLINI, MANUELA;RECANATINI, MAURIZIO;MELCHIORRE, CARLO
2007

Abstract

Alzheimer s disease (AD) is a complex multifactorial syndrome unlikely to arise from a single causal factor, but due to a number of different but related biological alterations that contribute to its pathogenesis. None of the presently marketed drugs, although valuable in improving cognitive, behavioral, and functional impairments, alter AD progression, and the goal of an effective disease-modifying treatment is still unmet. Nowadays, mechanism-based drug-design approaches are mainly directed toward two proteins, amyloid b (Ab) and tau. Ab is the core constituent of senile plaques, one of the key pathological characteristics of AD, whereas phosphorylated tau is the main component of neurofibrillary tangles, the other hallmark lesion of AD. Despite enormous research effort, no new molecules that interfere with the biochemical pathways of either Ab or tau have been approved so far for the treatment of AD. This failure is probably due to the weakness of the classic drug discovery approach based on the “one molecule, one target” paradigm, which might prove inadequate when the molecular complexity of the disease is addressed. In fact, the multifactorial nature of AD and the current lack of an accepted unitary theory to account for AD neurodegeneration have formed the basis of a growing consensus that single compounds are required that are able to interact with several molecular targets in the neurotoxic cascade (the innovative “one molecule, multiple targets” paradigm). Herein, we report on a new drug candidate (memoquin, patent pending) derived from a program aimed at creating multifunctional molecules to interfere with different key target points of AD neurodegeneration.
Cavalli A.; Bolognesi M. L.; Capsoni S.; Andrisano V.; Bartolini M.; Margotti E.; Cattaneo A.; Recanatini M.; Melchiorre C.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/46487
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