LEF kommentiert untenstehendes Paper:
"The group of scientists, led by Scintillon faculty members Stuart Lipton, MD, PhD, Rajesh Ambasudhan, PhD, and Tomohiro Nakamura, PhD, found that both excess sugar and beta-amyloid protein caused a rise in nitric oxide and other free radical species. This change led to the modification of multiple enzymes through a chemical process called S-nitrosylation. Because this modification changes enzymatic activity, it caused abnormal increases in both insulin and beta-amyloid protein. Moreover, the changes in enzyme activity led to damage of synapses, the region where nerve cells communicate with one another in the brain. The combination of high sugar and beta-amyloid protein caused the greatest loss of synapses. Since loss of synapses correlates with cognitive decline in Alzheimer’s, high sugar and beta-amyloid coordinately contribute to memory loss."
“This work points to a new common pathway to attack both Type 2 diabetes, along with its harbinger, metabolic syndrome, and Alzheimer’s disease,” stated Dr. Lipton, study leader and Distinguished Professor at Scintillon and a clinical neurologist at UC San Diego. “It also means that we now know these diseases are related on a molecular basis, and hence, they can be treated with new drugs on a common basis,” stated Dr. Ambasudhan, a senior author and Assistant Professor at the Scintillon Neurodegenerative Disease Center.
Also entweder dauerhaft erhöhte Glucosewerte oder Amyloid-Plaques (oder auch am "Besten": beide Faktoren zusammen) ändern Signalpfade derart, dass über erhöhten NO-Streß die Insulinsensitivität abnimmt und mehr Amyloid-Plaques gebildet werden. Mit der tendenziellen Folge: Diabetes II und Alzheimer. Das ist der Link, der die Benbachtungsstudien über Alzheimer als "Typ-3-Diabetes" auch molekular erklären kann.
Metabolic syndrome (MetS) and Type 2 diabetes mellitus (T2DM) increase risk for Alzheimer's disease (AD). The molecular mechanism for this association remains poorly defined. Here we report in human and rodent tissues that elevated glucose, as found in MetS/T2DM, and oligomeric β-amyloid (Aβ) peptide, thought to be a key mediator of AD, coordinately increase neuronal Ca(2+) and nitric oxide (NO) in an NMDA receptor-dependent manner. The increase in NO results in S-nitrosylation of insulin-degrading enzyme (IDE) and dynamin-related protein 1 (Drp1), thus inhibiting insulin and Aβ catabolism as well as hyperactivating mitochondrial fission machinery. Consequent elevation in Aβ levels and compromise in mitochondrial bioenergetics result in dysfunctional synaptic plasticity and synapse loss in cortical and hippocampal neurons. The NMDA receptor antagonist memantine attenuates these effects. Our studies show that redox-mediated posttranslational modification of brain proteins link Aβ and hyperglycaemia to cognitive dysfunction in MetS/T2DM and AD.