Neuro metab connections
Life-expectancy is increasing, that’s good news. The downside to this trend is that more and more people will develop diseases such as Diabetes or Alzheimer’s and some may even combine Diabetes AND Alzheimer.
In fact, epidemiologic studies have shown having type-2 diabetes increases the risk of developing Alzheimer’s disease by 65% and that 80% of Alzheimer patients have problems of glycemic control.
The “Metabrain Endeavour” is to prevent and treat these two interconnected diseases from a common angle. Here are some questions deserving to be addressed:
- How do metabolic states affect brain function?
- How can CNS targets expressed in the periphery regulate metabolism?
- How can anti-diabetic compounds contribute to preventing and treating neurodegenerative diseases?
The Metabrain Endeavour
The “Metabrain Hypothesis” is based on a series of observations taken from the scientific literature, plus a series of experiments carried-out by the Metabrain team:
- The hallmarks of the dementia associated with Alzheimer’s disease are memory loss and difficulties in learning. These same problems have been observed in diabetic states.
- ß amyloid deposits present in the brain of Alzheimer’s patients induce neuronal cell death. Structurally similar amyloid deposits are observed in the pancreas of diabetic patients and can also induce pancreatic cell death.
- Insulin and Insulin receptors are key to learning and memory. Insulin-resistance, the main defect affecting type-2 diabetic and obese patients, is also observed in the brain of Alzheimer’s patients.
- Indeed, amyloid ß oligomers (ADDLs) accumulation at brain synapses block the accumulation of insulin receptors at synapses and therefore reduce the cells sensitivity to insulin, resulting in difficulties in the memorization process.
- Advance Glycation End-products (AGE) are abnormally high in both type-2 diabetes and Alzheimer’s and represent an important source of inflammation and oxidative stress in the affected tissues.
- Neurons releasing neurotransmitters in the brain and pancreatic ß cells releasing insulin the bloodstream have many similarities, despite their different embryonic origin. They are both excitable cells which respond to chemical signals through a depolarization, which triggers the release or either insulin or neurotransmitters through a mechanism known as exocytosis. In addition, many enzymes involved in the biosynthesis of amino acids, hormones, cellular and nuclear receptors and cytoskeletal components are expressed in both types of cells.
Taken together, there is mounting evidence that scientist from the metabolic and CNS fields must unite to look at neurodegenerative processes from a different angle, taking into account the evidence generated whilst studying metabolic diseases. Conversely, knowledge generated in CNS labs could contribute to innovative way to prevent and treat metabolic diseases. This is precisely what Metabrain Research and its partners are doing.
If you share our interests and want to know more about our research,contact us.
References :
- Awad N, Gagnon M, Messier C ; The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function. J Clin Exp Neuropsychol. 26 :1044-1080, 2004
- De la Monte S ; Insulin resistance and Alzheimer’s disease. BMB Rep. 42:475-81., 2009
- Franco Ks, Bronson D; Diabetes mellitus and Alzheimer disease. Arch. Neurol. 62 : 330, 2005
- Janson J, Laedtke T, Parisi JE, O'Brien P, Petersen RC, Butler PC ; Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 53 : 474, 2004
- Scharfmann R, Czernichow P; Differentiation and growth of pancreatic beta cells. Diab. Metab. 22 : 223-228, 1996
- Van Harten B, de Leeuw FE, Weinstein HC, Scheltens P, Biessels GJ; Brain imaging in patients with diabetes: a systematic review. Diabetes Care. 29 : 2539-48, 2006
- Zhao WQ, Townsend M; Insulin resistance and amyloidogenesis as common molecular foundation for type 2diabetes and Alzheimer's disease. Biochimica et Biophysica Acta 1792 (2009) 482–496