RNA interference as a tool for Alzheimer's disease therapy.
RNA interference is a biological process that controls gene silencing in all living cells. Targeting the RNA interference system represents a novel therapeutic strategy able to intercede with multiple disease-related genes and to target many neurodegenerative diseases. Recently, the design of small interfering RNA-selective compounds has become more straightforward because of the significant progress made in predictive modeling for new therapeutic approaches. Although in vivo delivery of RNA interference remains a significant obstacle, new data show that RNAi blocks gene function in vivo, suggesting a potential therapeutic approach for humans. Some groups have demonstrated the efficacy of RNAi therapy in Alzheimer's disease. Results, based on animal models, show a down-regulation of the amyloid precursor protein and a consequent reduction of the amyloid-beta peptide accumulation in the brain or the inactivation of beta-secretase (BACE1). Indeed, lentiviral vectors expressing siRNAs targeting BACE1 reduce amyloid production and the neurodegenerative and behavioural deficit in APP transgenic mice. This review highlights recent advances in RNA research and focuses on strengths and weaknesses of RNAi compounds in Alzheimer's disease.
Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia, 64 Via del Fosso di Fiorano, 00143 Rome, Italy. a.orlacchio@hsantalucia.it
Antonio
A
Orlacchio
Giorgio
G
Bernardi
Aldo
A
Orlacchio
Sabata
S
Martino
D000544:Alzheimer Disease / Q000503:physiopathology / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D034622:RNA Interference / Q000187:drug effects*
D016564:Amyloid beta-Protein Precursor