Decisive role of Reelin signaling during early stages of Alzheimer’s disease
| Autor: | Tina Notter, Sandra Pfister, Irene Knuesel, Dimitrije Krstic |
|---|---|
| Přispěvatelé: | University of Zurich, Knuesel, I |
| Rok vydání: | 2013 |
| Předmět: |
Olfactory system
Cell Adhesion Molecules Neuronal 10050 Institute of Pharmacology and Toxicology Nerve Tissue Proteins 610 Medicine & health Disease Cellular level Alzheimer Disease Limbic System Animals Humans Effective treatment Reelin PI3K/AKT/mTOR pathway Neuroinflammation Extracellular Matrix Proteins biology General Neuroscience Serine Endopeptidases Brain 2800 General Neuroscience Long-term potentiation Olfactory Pathways Reelin Protein Early Diagnosis biology.protein 570 Life sciences Nerve Net Psychology Neuroscience Signal Transduction |
| Zdroj: | Neuroscience |
| ISSN: | 0306-4522 |
| Popis: | Alzheimer's disease (AD) is one of the largest unmet medical concerns of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles, the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiological characteristic of late-onset AD. |
| Databáze: | OpenAIRE |
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