Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease that is increasingly becoming a global threat to the health and life of the elderly worldwide. Although there are some drugs clinically available for treating PD, these treatments can only alleviate the symptoms of PD patients but cannot completely cure the disease. Therefore, exploring other potential mechanisms to develop more effective treatments that can modify the course of PD is still highly desirable. Over the last two decades, histone deacetylases, as an important group of epigenetic targets, have attracted much attention in drug discovery. This review focused on the current knowledge about histone deacetylases involved in PD pathophysiology and their inhibitors used in PD studies. Further perspectives related to small molecules that can inhibit or degrade histone deacetylases to treat PD were also discussed.

The search for effective neuroprotective agents for the treatment of neurotrauma has always been of great interest to researchers around the world. Extracellular heat shock protein 70 (eHsp70) is considered a promising agent to study, as it has been demonstrated to exert a significant neuroprotective activity against various neurodegenerative diseases. We showed that eHsp70 can penetrate neurons and glial cells when added to the incubation medium, and can accumulate in the nuclei of neurons and satellite glial cells after axotomy. eHsp70 reduces apoptosis and necrosis of the glial cells, but not the neurons. At the same time, co-localization of eHsp70 with p53 protein, one of the key regulators of apoptosis, was noted. eHsp70 reduces the level of the p53 protein apoptosis promoter both in glial cells and in the nuclei and cytoplasm of neurons, which indicates its neuroprotective effect. The ability of eHsp70 to reverse the proapoptotic effect of the p53 activator WR1065 may indicate its ability to regulate p53 activity or its proteosome-dependent degradation.

Sirtuins (SIRTs) are NAD+- dependent histone deacetylases. They are involved in a variety of biological pathways and are thought to be a promising target for treating several human disorders. Although evidence is piling up to support the neuroprotective role of SIRTs in ischemic stroke, the role of different sirtuin isoforms needs further investigation. We studied the effects of photothrombotic stroke (PTS) on the expression and localization of sirtuins SIRT1 and SIRT2 in neurons and astrocytes of the penumbra and tested the activity of their selective and non-selective inhibitors. SIRT1 levels significantly decreased in the penumbra cells nuclei and increased in their cytoplasm. This indicated a redistribution of SIRT1 from the nucleus to the cytoplasm after PTS. The expression and intracellular distribution of SIRT1 were also observed in astrocytes. Photothrombotic stroke caused a sharp increase in SIRT2 levels in the cytoplasmic fraction of the penumbra neurons. SIRT2 was not expressed in the penumbra astrocytes. SIRT1 and SIRT2 did not co-localize with TUNEL-positive apoptotic cells. Mice were injected with EX-527, a selective SIRT1 inhibitor; SirReal2, selective SIRT2 inhibitor or salermide, a nonspecific inhibitor of SIRT1 and SIRT2. These inhibitors did not demonstrate any change in the infarction volume or the apoptotic index, compared to the control samples. The studies presented indicate the involvement of these sirtuins in the response of brain cells to ischemia in the first 24 h, but the alterations in their expression and change in the localization of SIRT1 are not related to the regulation of penumbra cell apoptosis in the acute period after PTS.

Neurotrauma is among the main causes of human disability and mortality. The transcription factor E2F1 is one of the key proteins that determine the fate of cells. The involvement of E2F1 in the regulation of survival and death of peripheral nerve cells after axotomy has not been previously studied. We, for the first time, studied axotomy-induced changes in the expression and localization of E2F1 following axonal injury in rats and crayfish. Immunoblotting and immunofluorescence microscopy were used for the analysis of the expression and intracellular localization of E2F1 and its changes after axotomy. To evaluate whether this transcription factor promotes cell apoptosis, we examined the effect of pharmacological inhibition of E2F activity in axotomized rat models. In this work, axotomy caused increased expression of E2F1 as early as 4 h and even 1 h after axotomy of mechanoreceptor neurons and ganglia of crayfish ventral nerve cord (VNC), as well as rat dorsal root ganglia (DRG). The level of E2F1 expression increased both in the cytoplasm and the nuclei of neurons. Pharmacological inhibition of E2F demonstrated a pronounced neuroprotective activity against axotomized DRGs. E2F1 and downstream targets could be considered promising molecular targets for the development of potential neuroprotective agents.

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