Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

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New Proposals for Treatment Sporadic Alzheimers Disease

Author(s): Ryszard Pluta, Marzena Ulamek.

Abstract:

Patients with sporadic Alzheimers disease develop a progressive dementia in adulthood, accompanied by five main changes in the brain: loss of neurons, accumulation of intraneuronal neurofibrillary tangles and development of amyloid plaques and deposition of amyloid in neurovessels and inflammation response. Alzheimers disease is the major form of dementia and the fourth leading cause of death in aging population. The study of neurobiology and treatment of Alzheimers disease, now more than ever, needs an infusion of a new concept. The goals of this paper are to review knowledge of the influence amyloid and ischemic alterations on final development of Alzheimers disease, especially with regards to the pathogenesis of Alzheimers disease plaques, to develop a consensus on whether ischemic blood-brain barrier permeability for amyloid peptide or both are a valid target for Alzheimers disease therapy. Alzheimers disease today desperately needs to be treated; we can recently neither prevent nor cure it. Analyzing an experimental models of Alzheimers disease, we will address the issue whether plaques of amyloid persist, develop with time, or both in animals injected with β-amyloid peptide. The strict reasons for this disease now are not known, but recent evidence suggests that the ischemic factors play an important role. Based on above suggestions recent direct evidence that amyloid plaques and neurofibrillary tangles can be cleared from the brain is thus provided in experimental condition. Additionally recent study provides data that immunization with β-amyloid peptide decreases blood-brain barrier permeability for β-amyloid peptide or restores blood-brain barrier integrity. This information suggests that the preventative effect of peptide aggregation, as well as the solubilization of already formed plaques by site-directed amyloid antibody is simple explanation of the removal process. Possible mechanism of action is that anti-amyloid antibodies facilitate clearance of amyloid through blood-brain barrier after plaques formation.

Keywords: Alzheimer's disease, ischemia, immunotherapy, blood-brain barrier, gene therapy, amyloid, tau protein, plaques, tangles

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Article Details

VOLUME: 8
ISSUE: 4
Year: 2008
Page: [286 - 296]
Pages: 11
DOI: 10.2174/187152408786848148
Price: $58