Neuroscience | NMDA receptor & Alzheimer’s disease скачать в хорошем качестве

Neuroscience | NMDA receptor & Alzheimer’s disease

Note error typo. Plaques to tangles (not correct ) NMDA receptor important for learning and memory. Works with AMPA receptor. NMDA receptor is blocked by Magnesium. Calcium enters and causes changes in the cell. More AMPA receptors get added (short term) Later changes there changes in gene expression via CREB. • Drugs that target it include: • Ketamine (recently approved for certain types of depression) (Spravato) (Esketamine generic) (S enantiomer) (has to do with structure’s 3D shape, analogous to right hand vs left. Identical but oriented in opposite direction. May vary effect because of the shape of the receptors and where those receptors are distributed. • PCP (street drug) • Memantine (used to treat Alzheimer’s disease (later stages)) • (Mg2+ sold as a supplement in various formulations that vary in effect) Agonist = promotes activity Antagonist blocks activity • How does it help with Alzheimer’s? • Too much glutamate can cause neurons to die Via: excitotoxicity: Ca2+ levels must be kept low so too much excitation can cause too much calcium to enter. Ca2+ cause changes inside the cell that can lead the initiation apoptosis. (programmed cell death) Memantine therefore works by preventing excess glutamate from overexciting the neuron. Alzheimer’s Dx: Clinical history and tests e.g Moca (not the drink) (Montreal cognitive assessment) Risk factors: Age, genetics (APOE4) and environment (head injuries) as with many other diseases. Neurodegenerative disease • Mechanism 1: Amyloid precursor protein is a normal protein that can incorrectly cut and create problems  Amyloid plaques  Tangles (cause all kinds of problems when they accumulate) • Mechanism 2: Phosphorylated Tau  neurofibrillary tangles • (neurons have roads (microtubules) in them where NT are carried, and the tau is like the glue when it gets a certain chemical modification (phosphorylation) the glue no longer hold the road together rather it adheres to itself and forms these tangles. • Overall: alter neuronal signaling (inside and outside the neuron and lead to loss of neurons due to these disturbances) • Neuronal loss via mechanisms like: ROS (generated from microglia activation) Caspase activation  apoptosis Image : https://www.webmd.com/drugs/2/drug-77...