Search

Prohibitins (PHBs) are conserved proteins in eukaryotic cells, which are mainly located in the inner mitochondrial membrane (IMM), cell nucleus, and cell membrane. PHBs play crucial roles in various cellular functions, including the cell cycle regulation, tumor suppression, immunoglobulin M receptor binding, and aging. In addition, recent in vitro and in vivo studies have revealed that PHBs are important in nervous system diseases. PHBs can prevent apoptosis, inflammation, mitochondrial dysfunction, and autophagy in neurological disorders through different molecules and pathways, such as OPA-1, PINK1/Parkin, IL6/STAT3, Tau, NO, LC3, and TDP43. Therefore, PHBs show great promise in the protection of neurological disorders. This review summarizes the relevant studies on the relationship between PHBs and neurological disorders and provides an update on the molecular mechanisms of PHBs in nervous system diseases.

Lewy bodies are characteristic spherical inclusions in Parkinson's disease (PD) that are formed by α-synuclein fibrils. Ferruginol (Fer) is an amonomeric compound isolated from a traditional Chinese herb. Here, we show that Fer exerted potent neuroprotective effects in both in vitro and in vivo PD models. Neuronal cells transfected with A53T mutant (A53T) α-synuclein plasmids and treated with Fer exhibited attenuated the cytotoxicity induced by pathogenic A53T α-synuclein overexpression. Further, when we transfected neuronal cells with siRNA-SNCA (alpha-synuclein) plasmids and incubated them with Fer, the protective role of Fer decreased. We also found that Fer was a potent α-synuclein inhibitor in neuronal cells, which promotes the clearance of αsynuclein in dopaminergic neurons exposed to 1-Methyl-4-phenylpyridinium (MPP +). Fer could inhibit abnormal α-synuclein aggregation and dopaminergic neuron depletion in A53T-Tg mice, suggesting that a role for Fer in α-synuclein accumulation and nigrostriatal pathway injury. Our study revealed that Fer strongly alleviated neurodegeneration by promoting α-synuclein clearance, indicating a neuroprotective role against α-synuclein oligomer-induced neurodegeneration, which makes it a promising candidate for the treatment of PD and other neurodegenerative diseases.