Botulinum toxin causes flaccid paralysis by which molecular mechanism at the cholinergic nerve terminal?

• A Blockade of choline reuptake into the terminal
• B Blockade of postsynaptic nicotinic receptors at the motor endplate
• C Inhibition of acetylcholinesterase at the synaptic cleft
• D Proteolytic cleavage of SNARE proteins required for fusion of acetylcholine vesicles with the presynaptic membrane ✓

Explanation

Botulinum toxin is internalized into cholinergic terminals where its light chain acts as a zinc-dependent endopeptidase, cleaving SNARE proteins such as SNAP-25, syntaxin or synaptobrevin depending on serotype. Vesicle docking and fusion fail, so acetylcholine release ceases and flaccid paralysis results. It does not affect choline transport, cholinesterase activity or the postsynaptic receptor, which distinguishes it from hemicholinium, anticholinesterases and curare respectively.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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