Emerging targets in neurodegeneration: new opportunities for Alzheimer's disease treatment?
Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the brain associated with memory impairment, progressive cognitive decline and changes in personality and behavior, with rising incidence among elderly people. Reflecting the world population ageing, the scenario is expected to worsen in the next decades if novel drugs or mechanisms that help to counteract neurodegeneration will not be identified. The complex neuropathology of AD is characterized by cholinergic loss, extracellular deposition of amyloid-β plaques, formation of intracellular neurofibrillary tangles, chronic brain inflammation and oxidative damage. To date, there are no effective treatments that can slow or halt the disease, and currently approved drugs only seem to act as palliative by temporary ameliorating cognitive impairment. On the other hand, the role played by other biological systems in the pathogenetic process is now clearly growing and, as knowledge on how AD develops and triggers brain damage proceeds, drug discovery attempts to identify new potential therapeutic targets. This review will focus on these emerging strategies, some of which could open new therapeutic perspectives in Alzheimer's disease, adding new elements for the medicinal chemist to handle and combine for the design of novel multi-target-directed ligands able to simultaneously modulate 'old classic' and newly identified targets.
Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. angela.rampa@unibo.it
Angela
A
Rampa
Silvia
S
Gobbi
Federica
F
Belluti
Alessandra
A
Bisi
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D063386:Cannabinoid Receptor Agonists / Q000138:chemical synthesis* / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000627:therapeutic use; D006801:Humans; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D018384:Oxidative Stress; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D058225:Plaque, Amyloid / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D043882:Receptors, Cannabinoid / Q000378:metabolism
D063386:Cannabinoid Receptor Agonists; D056572:Histone Deacetylase Inhibitors; D018697:Nootropic Agents; D047495:PPAR gamma; D043882:Receptors, Cannabinoid; D053829:Amyloid Precursor Protein Secretases