- ホーム
- > 洋書
- > 英文書
- > Science / Mathematics
Full Description
Epilepsy affects approximately 3% of the population, and is usually defined as a tendency to experience recurrent seizures arising from periodic neuronal hyperexcitability of unknown causes. Different genetic factors, through various mechanisms, can cause this abnormal neuronal behavior. The etiology of epilepsy is a major determinant of clinical course and prognosis. Many of the genes that have been implicated in idiopathic epilepsies code for ion channels, whereas a wide spectrum of syndromes where epilepsy is a main clinical feature are caused by mutated genes that are involved in functions as diverse as cortical development, brain malformations, mitochondrial function, and cell metabolism. Similarly, different conditions as hypoxia, trauma, infections, or metabolic unbalances can develop epileptic syndromes where upregulation of several genes could be related to the epileptogenic mechanisms. The most common human genetic epilepsies display a complex pattern of inheritance, and the susceptible genes are largely unknown. However, major advances have recently been made in our understanding of the genetic basis of monogenic inherited epilepsies. As we continue to unravel the molecular genetic basis for epilepsies, it will increasingly influence their classification and diagnosis. A majority of epileptic patients may control their crisis with anticonvulsant drugs, however 30%-40% became refractory to pharmacological therapies and require surgical treatment. The challenge of the molecular revolution will be the design of the best treatment protocols based on genetic profiles that include both the specific mechanistic etiology of the epilepsies, as well as their potential refractory behavior to current medications. This includes also the design of new therapeutic agents and targets, so as to reduce the number of cases with refractory epilepsy and epileptogenesis, and perhaps avoid the current surgical treatment (a procedure that was first described more than 4000 years ago) except as a last option.
Contents
Introduction
What Is Epilepsy?
Resting Potential
Action Potential
Are There Any Genetic Bases for Epilepsy?
Ligand-gated Ion Channels
Acetylcholine Receptors CHRNA4, CHRNB2, and CHRNA2
Ion Channels
Sodium Channels
Potassium Channel Subunit Mutations with LOF Effects
Voltage-gated Calcium Channel Mutations and Genetic Susceptibility
GABA Receptor Subunit Mutations (Chloride Channel)
Copy Number Variants and Comorbidities
Susceptibility Genes for Complex Epilepsy
Glycine Receptors
Ionotropic Glutamate Receptors
G-protein-coupled Receptors
Metabotropic Glutamate Receptors
Other Genetic Causes of Epilepsy
Mitochondrial Inheritance and Myoclonic Epilepsy with Ragged Red Fibers
Leucine-rich Glioma Inactivated Gene 1 (LGI1)
Inborn Errors of Metabolism and Epilepsy
Epilepsy and NMDs
FOLR1 Gene Mutation
Lysosomal Storage Disorders
The Solute-carrier Gene Superfamily and Epilepsy
Genes Related with Different Epileptic Syndromes
Genetic Mechanisms of Drug Resistance in Epilepsy
Definition of Drug Resistance in Epilepsy
Genetics of Drug Response in Epilepsy
Drug Transport System
ABC Transporters
ABC Transporters and RE
MDR1 (ABCB1) Gene Variants
The BBB's Role in Pharmacoresistance in Epilepsy
Induction of ABC Transporters: Is the Acquired Refractoriness an Inducible Process?
Genes and Pharmacodynamic Modifications
Inducing the Expression of P-gp in Neurons: Is it to Induce Epileptogenesis?
References
Author Biographies
