Neurodegeneration is associated to changes in serum insulin-like growth factors.
Serum levels of insulin and insulin-like growth factors and their binding proteins (IGFs and IGFBPs, respectively) are changed in human neurodegenerative diseases of very different etiology, such as Alzheimer's disease, amyotrophic lateral sclerosis, or cerebellar ataxia. However, the significance of these endocrine disturbances is not clear. We now report that in two very different inherited neurodegenerative conditions, ataxia-telangiectasia (AT) and Charcot-Marie-Tooth 1A (CMT-1A) disease, serum levels of IGFs are also altered. Both types of patients have increased serum IGF-I and IGFBP-2 levels, and decreased serum IGFBP-1 levels, while only AT patients have high serum insulin levels. Furthermore, serum IGFs are also changed in three different animal models of neurodegeneration: neurotoxin-induced motor discoordination, diabetic neuropathy, and hereditary cerebellar ataxia. In these three models, serum insulin levels are significantly decreased, serum IGF-I and IGFBP-1, -2, and -3 are decreased in diabetic and neurotoxin-injected rats, while serum IGFBP-1 is increased in hereditary ataxic rats. Altogether, these observations indicate that a great variety of neurodegenerative diseases show endocrine perturbations, resulting in changes in serum IGFs levels. These perturbations are disease-specific and are probably due to metabolic and endocrine derangements, nerve cell death, and sickness-related disturbances associated to the neurodegenerative process. Our observations strongly support the need to evaluate serum IGFs in other neurodegenerative conditions.
Busiguina
S
S
Laboratory of Neuroendocrinology, Cajal Institute, Madrid, Spain.
Fernandez
A M
AM
Barrios
V
V
Clark
R
R
Tolbert
D L
DL
Berciano
J
J
Torres-Aleman
I
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001260:Ataxia Telangiectasia / Q000097:blood* / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002524:Cerebellar Ataxia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000097:blood* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications; D003929:Diabetic Neuropathies / Q000097:blood / Q000209:etiology; D004195:Disease Models, Animal; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011725:Pyridines; D051381:Rats; D011922:Rats, Mutant Strains; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D009185:Myelin Proteins; C073687:PMP22 protein, human; C489546:Pmp22 protein, rat; D011725:Pyridines; D025521:Tumor Suppressor Proteins; C010835:3-acetylpyridine; D007334:Insulin-Like Growth Factor I; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases