Pharmacogenomics of neurodegenerative diseases.
Current knowledge of sporadic degenerative disorders suggests that, despite their multifactorial etiopathogenesis, genetics plays a primary role in orchestrating the pathological events, and even dramatically changes the disease phenotype from patient to patient. Genes may act as susceptibility factors, increasing the risk of disease development, or may operate as regulatory factors, modulating the magnitude and severity of pathogenic processes or the response to drug treatment. The goal of pharmacogenomics is the application of this knowledge to elaborate more specific and effective treatments and to tailor therapies to individual patients according to their genetic profile. Here, we outline the leading theories on the etiopathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer disease, and we review the potential role of genetic variations, such as gene mutations and polymorphisms, in each context. We also suggest potential targets for new therapeutic approaches and variability factors for current treatments based on genotype features. Finally, we propose a few options of preventive therapeutic interventions in patients with a high genetic risk of disease.
Maimone
D
D
Department of Neurology, Ospedale Garibaldi, Piazza S. Maria di Gesù 5, 95123 Catania, Italy.
Dominici
R
R
Grimaldi
L M
LM
D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018377:Neurotransmitter Agents / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents