The many Neurofaces of Prohibitins 1 and 2: Crucial for the healthy brain, dysregulated in numerous brain disorders

Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are proteins that are nearly ubiquitously expressed. They are localized in mitochondria, cytosol and cell nuclei. In the healthy CNS, they occur in neurons and non-neuronal cells (oligodendrocytes, astrocytes, microglia, and endothelial cells) and fulfill pivotal functions in brain development and aging, the regulation of brain metabolism, maintenance of structural integrity, synapse formation, aminoacidergic neurotransmission and, probably, regulation of brain action of certain hypothalamicpituitary hormones.With regard to the diseased brain there is increasing evidence that prohibitins are prominently involved in numerous major diseases of the CNS, which are summarized and discussed in the present review (brain tumors, neurotropic viruses, Alzheimer disease, Down syndrome, Fronto-temporal and vascular dementia, dementia with Lewy bodies, Parkinson disease, Huntington disease, Multiple sclerosis, Amyotrophic lateral sclerosis, stroke, alcohol use disorder, schizophrenia and autism). Unfortunately, there is no PHB-targeted therapy available for any of these diseases.

Automated summary

Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are widely expressed proteins localized in mitochondria, cytosol, and cell nuclei. They play important roles in brain development, aging, metabolism regulation, structural integrity maintenance, synapse formation, neurotransmission, and the action of hypothalamic-pituitary hormones. However, they are also involved in various major diseases of the CNS, for which there is currently no targeted therapy available.