Neurotrophic factors in Huntington's disease.
Huntington's disease is a neurodegenerative disorder characterized by the selective loss of striatal neurons and, to a lesser extent, cortical neurons. The neurodegenerative process is caused by the mutation of huntingtin gene. Recent studies have established a link between mutant huntingtin, excitotoxicity and neurotrophic factors. Neurotrophic factors prevent cell death in degenerative processes but they can also enhance growth and function of neurons that are affected in Huntington's disease. The endogenous regulation of the expression of neurotrophic factors and their receptors in the striatum and its connections can be important to protect striatal cells and maintains basal ganglia connectivity. The administration of exogenous neurotrophic factors, in animal models of Huntington's disease, has been used to characterize the trophic requirements of striatal and cortical neurons. Neurotrophins, glial cell line-derived neurotrophic factor family members and ciliary neurotrophic factor have shown a potent neuroprotective effects on different neuronal populations of the striatum. Furthermore, they are also useful to maintain the integrity of the corticostriatal pathway. Thus, these neurotrophic factors may be suitable for the development of a neuroprotective therapy for neurodegenerative disorders of the basal ganglia.
Alberch
Jordi
J
Department of Cell Biology and Pathology, Medical School, IDIBAPS, University of Barcelona, Casanova 143, E-08036 Barcelona, Spain. alberch@medicina.ub.es
Pérez-Navarro
Esther
E
Canals
Josep M
JM
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism / Q000627:therapeutic use; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases