Tubulin polyglutamylation, a regulator of microtubule functions, can cause neurodegeneration

Neurodegenerative diseases lead to a progressive demise of neuronal functions that ultimately results in neuronal death. Besides a large variety of molecular pathways that have been linked to the degeneration of neurons, dysfunctions of the microtubule cytoskeleton are common features of many human neurodegenerative disorders. Yet, it is unclear whether microtubule dysfunctions are causative, or mere bystanders in the disease progression. A so-far little explored regulatory mechanism of the microtubule cytoskeleton, the posttranslational modifications of tubulin, emerge as candidate mechanisms involved in neuronal dysfunction, and thus, degeneration. Here we review the role of tubulin polyglutamylation, a prominent modification of neuronal microtubules. We discuss the current understanding of how polyglutamylation controls microtubule functions in healthy neurons, and how deregulation of this modification leads to neurodegeneration in mice and humans.