Connecting the Neurobiology of Developmental Brain Injury: Neuronal Arborisation as a Regulator of Dysfunction and Potential Therapeutic Target

Neurodevelopmental disorders can derive from a complex combination of genetic variation and environmental pressures on key developmental processes. Despite this complex aetiology, and the equally complex array of syndromes and conditions diagnosed under the heading of neurodevelopmental disorder, there are parallels in the neuropathology of these conditions that suggest overlapping mechanisms of cellular injury and dysfunction. Neuronal arborisation is a process of dendrite and axon extension that is essential for the connectivity between neurons that underlies normal brain function. Disrupted arborisation and synapse formation are commonly reported in neurodevelopmental disorders. Here, we summarise the evidence for disrupted neuronal arborisation in these conditions, focusing primarily on the cortex and hippocampus. In addition, we explore the developmentally specific mechanisms by which neuronal arborisation is regulated. Finally, we discuss key regulators of neuronal arborisation that could link to neurodevelopmental disease and the potential for pharmacological modification of arborisation and the formation of synaptic connections that may provide therapeutic benefit in the future.

ХЕМОСЕНСИБИЛИЗАЦИЯ ОПУХОЛЕВЫХ КЛЕТОК ФЕНОЛЬНЫМИ АНТИОКСИДАНТАМИ: РОЛЬ ФАКТОРА ТРАНСКРИПЦИИ NRF2

Pharmacological modification of the redox properties of tumor cells is a promising approach to enhance the efficiency of antitumor therapy. Currently, the transcription factor Nrf2 is considered as a new target for the development of selective chemosensitizers. Nrf2 plays a key role in regulation of cellular redox homeostasis against stress and during adaptation processes. Many natural and synthetic phenolic antioxidants are inducers of Nrf2 transcriptional activity. Due to differences in Nrf2 transcriptional activity between normal and tumor cells, phenolic antioxidants at certain concentrations act as biological regulators the antioxidant activity of which has two different effects: in tumor cells they promote the development of oxidative stress and enhance the effect of antitumor drugs, in normal cells these antioxidants exhibit protective properties. The review discusses the possible molecular mechanisms of action and the prospects for the clinical use of natural and synthetic phenolic antioxidants in antitumor therapy.