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The neuronal membrane as a key factor in neurodegeneration

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The neuronal membrane plays a crucial role in a plethora of processes involved in cell preservation, and numerous events observed in different neuropathologies are a consequence of membrane dysregulation and dysfunctioning.
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The neuronal membrane plays a crucial role in a plethora of processes involved in cell preservation, and numerous events observed in different neuropathologies are a consequence of membrane dysregulation and dysfunctioning.

Mounting evidence suggests that the plasma membrane is involved in the regulation of the main hallmarks leading to neurodegeneration in diseases such as Alzheimer’s disease, Parkinson’s disease, synucleopathies, prion diseases, and other dementias. Indeed, abnormal processing of protein markers known to interact with the plasma membrane such as amyloid precursor protein, alpha-synuclein and prion protein is predicted to lead to pathological changes in their binding properties and function. Some of these markers are present in pathologically high amounts or in a modified form with enhanced membrane association, oligomerization and molecular processing. This causes neuronal impairment leading to a variety of adverse effects including impaired neuronal trafficking, heightened oxidative stress and defects in lipid metabolism. Furthermore, different ion channels and neurotransmitter receptors known to influence the development of brain disorders, e.g. glutamate receptors and GABA receptors, appear to be profoundly affected by plasma membrane alterations. Interestingly, emerging data reveal that lipid composition and dynamics in particular in membrane microdomains may be at the basis of these impairments.

A comprehensive survey of the mechanisms related to the interaction of different neuropathological targets with the plasma membrane, and the consequences of the loss of membrane homeostasis in the function of proteins involved in neurodegenerative disorders may be an interesting topic for FMPB readers.


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