Novel strategies for Alzheimer's disease treatment

Abstract

Considerable progress has been made in recent years towards better understanding the pathogenesis of Alzheimer's disease (AD), a dementing neurodegenerative disorder that affects > 10 million individuals in the US and Europe combined. Recent studies suggest that alterations in the processing of amyloid precursor protein (APP), resulting in the accumulation of amyloid-β protein (Aβ) and the formation of oligomers leads to synaptic damage and neurodegeneration. Therefore, strategies for treatment development have been focused on reducing Aβ accumulation using, among other approaches, antiaggregation molecules, regulators of the APP proteolysis and processing, reducing APP production (e.g., small-interfering RNA), and increasing Aβ clearance with antibodies, apolipoprotein E and Aβ-degrading enzymes (e.g., neprilysin). The main focus of this review is on novel treatments for AD with a special emphasis on delivering neuroprotective and antiamyloidogenic molecules by gene therapy and by promoting neurogenesis.

Keywords::

• Alzheimer's disease
• amyloid
• apolipoprotein E
• blood–brain barrier
• cerebrolysin
• gene therapy
• neprilysin
• plaques
• siRNA
• tangles
• tau

Acknowledgements

This work was supported by NIH grants AG18440, AG10435 and AG022074.

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