Novel strategies for Alzheimer's disease treatment.
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-beta protein (Abeta) and the formation of oligomers leads to synaptic damage and neurodegeneration. Therefore, strategies for treatment development have been focused on reducing Abeta accumulation using, among other approaches, antiaggregation molecules, regulators of the APP proteolysis and processing, reducing APP production (e.g., small-interfering RNA), and increasing Abeta clearance with antibodies, apolipoprotein E and Abeta-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.
Spencer
Brian
B
University of California, Department of Neurosciences, San Diego, La Jolla, CA 92093-0624, USA.
Rockenstein
Edward
E
Crews
Leslie
L
Marr
Robert
R
Masliah
Eliezer
E
D000544:Alzheimer Disease / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D006801:Humans; D015260:Neprilysin / Q000008:administration & dosage / Q000502:physiology / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000502:physiology / Q000627:therapeutic use
D034741:RNA, Small Interfering; D015260:Neprilysin