ABSTRACT
The insulin-like growth factor (IGF) system has paracrine and endocrine roles in the central nervous system. There is evidence that IGF signalling pathways have roles in the pathophysiology of neurodegenerative disease. This review focusses on Alzheimer's disease and Parkinson's disease, the two most common neurodegenerative disorders that are increasing in prevalence globally in relation to the aging population and the increasing prevalence of obesity and type 2 diabetes. Rodent models used in the study of the molecular pathways involved in neurodegeneration are described. However, currently, no animal model fully replicates these diseases. Mice with triple mutations in APP, PSEN and MAPT show promise as models for the testing of novel Alzheimer's therapies. While a causal relationship is not proven, the fact that age, obesity and T2D are risk factors in both strengthens the case for the involvement of the IGF system in these disorders. The IGF system is an attractive target for new approaches to management; however, there are gaps in our understanding that first need to be addressed. These include a focus beyond IGF-I on other members of the IGF system, including IGF-II, IGF-binding proteins and the type 2 IGF receptor.
Subject(s)
Neurodegenerative Diseases , Humans , Animals , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/genetics , Alzheimer Disease/etiology , Alzheimer Disease/pathology , Signal Transduction , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor I/genetics , Somatomedins/metabolism , Disease Models, Animal , Parkinson Disease/metabolism , Parkinson Disease/genetics , Insulin-Like Growth Factor Binding Proteins/metabolism , Insulin-Like Growth Factor Binding Proteins/genetics , Insulin-Like PeptidesABSTRACT
The insulin-like growth factors (IGF-I and IGF-II) and their receptors are widely expressed in nervous tissue from early embryonic life. They also cross the blood brain barriers by active transport, and their regulation as endocrine factors therefore differs from other tissues. In brain, IGFs have paracrine and autocrine actions that are modulated by IGF-binding proteins and interact with other growth factor signalling pathways. The IGF system has roles in nervous system development and maintenance. There is substantial evidence for a specific role for this system in some neurodegenerative diseases, and neuroprotective actions make this system an attractive target for new therapeutic approaches. In developing new therapies, interaction with IGF-binding proteins and other growth factor signalling pathways should be considered. This evidence is reviewed, gaps in knowledge are highlighted, and recommendations are made for future research.
ABSTRACT
Branched-chain amino acids (BCAA) are used as nutritional support for patients with a range of conditions including liver cirrhosis and in-born errors of amino acid metabolism, and they are commonly used "sports" or exercise supplements. The effects of the BCAA on the in-vitro activity of calf intestinal alkaline phosphatase (EC. 3.1.3.1) were studied. All three BCAA were found to be uncompetitive inhibitors of the enzyme with L-leucine being the most potent ( = 24.9 mmol/L) and L-valine, the least potent ( = 37 mmol/L). Mixed BCAA are able to act in combination to inhibit the enzyme. Given the important role of intestinal alkaline phosphatase in gut homeostasis, these findings have potential implications for those taking high levels of BCAA as supplements.
Subject(s)
Alkaline Phosphatase/antagonists & inhibitors , Amino Acids, Branched-Chain/pharmacology , Animals , Cattle , Dietary Supplements , Leucine/pharmacology , Valine/pharmacologyABSTRACT
Based on my experiences, I have a few recommendations to implement in a hospital and a radiology department: Recognize that your staff is the most important resource and invest in them. Adopt the "KIT Procedure". Remember that physicians need positive feedback, too. Make sure that high windows and ceilings are clean and repaired. Maintain safe and comfortable wheelchairs. Make training and inservices in your department a priority. Find a way for patients and technologists to make eye contact during an MRI. The radiology administrator should emulate the CNO described and spend a day on a regular basis with staff. I recently spent 10 days in a hospital as a patient. During my stay, I learned how hospitals really operate and I passed along a few recommendations that I hope you find helpful. I plan to implement these recommendations in my facility. "In your day, like mine, Stay Strong!"--Adapted from my friend Bubby Greene.
