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Postmitotic neurons cannot use the often-used biologic solution of redundancy and selection to produce enough cells that still work correctly. Old neurons function in an oxidative environment requiring replacement of damaged proteins and organelles. Furthermore, the production of these proteins, and probably organelles, is not without synthetic errors. If the type of errors and damage were predictable, we might expect that specific remediation systems would have evolved. Because new ways are likely to appear as different exposures occur, a better solution is to have simple systems that recognize “bad” proteins/molecules.
The cells of all metazoans already have such a system used as a first line of defense against bad/foreign proteins and other molecules. The system is called innate immunity. Variations on this system probably play a key role in recognizing bad proteins.
There is growing support for the concept that neurodegeneration can be caused by problems in recognition and remediation of bad proteins. In many neurodegenerative diseases, proteins aggregate into insoluble clumps.1 These aggregated …
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