PHAR 562 Lecture Notes - Lecture 20: Motor Neuron Disease, Neurofibrillary Tangle, Tauopathy
12 Feb 2020
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Document Summary
Als is a motor neuron disease with degeneration of motor neurons innervating essential muscles. Riluzole acts on multiple proteins in the synapse, decreases glutamate concentration in the synaptic cleft. Inhibits glutamate release, inhibits voltage-dependent na+ & ca2+ channels, blocks nmda-rs, promotes eeat-mediated glutamate uptake. Several molecular mechanisms implicated in als: excitotoxicity, oxidative stress, er stress from protein misfolding upr & erad, decreased waste/aggregate clearance. Sod1 detoxifies superoxides, protects cells from oxidative stress. The glymphatic system: astrocytes play a significant role in als. In the brain, there is perivascular space between astrocyte end feet & capillaries: astrocyte end feet have aquaporins (water-transporting channels): promote fluid flow to wash away waste products (protein aggregates) from the brain. Promote exchange between csf & interstitial spinal fluid. A common theme in all neurodegenerative diseases: presence of protein aggregates: protein folding follows an energy landscape plaque forms, it cannot be reversed)
