Calcium-Associated Proteins in Neuroregeneration

The dysregulation of intracellular calcium levels is a critical factor in neurodegeneration, leading to the aberrant activation of calcium-dependent processes and, ultimately, cell death. Ca2+ signals vary in magnitude, duration, and the type of neuron affected. A moderate Ca2+ concentration can initiate certain cellular repair pathways and promote neuroregeneration. While the peripheral nervous system exhibits an intrinsic regenerative capability, the central nervous system has limited self-repair potential. There is evidence that significant variations exist in evoked calcium responses and axonal regeneration among neurons, and individual differences in regenerative capacity are apparent even within the same type of neurons. Furthermore, some studies have shown that neuronal activity could serve as a potent regulator of this process. The spatio-temporal patterns of calcium dynamics are intricately controlled by a variety of proteins, including channels, ion pumps, enzymes, and various calcium-binding proteins, each of which can exert either positive or negative effects on neural repair, depending on the cellular context. In this concise review, we focus on several calcium-associated proteins such as CaM kinase II, GAP-43, oncomodulin, caldendrin, calneuron, and NCS-1 in order to elaborate on their roles in the intrinsic mechanisms governing neuronal regeneration following traumatic damage processes

Vitamin C Modes of Action in Calcium-Involved Signaling in the Brain

Vitamin C (ascorbic acid) is well known for its potent antioxidant properties, as it can neutralize ROS and free radicals, thereby protecting cellular elements from oxidative stress. It predominantly exists as an ascorbate anion and after oxidation to dehydroascorbic acid and further breakdown, is removed from the cells. In nervous tissue, a progressive decrease in vitamin C level or its prolonged deficiency have been associated with an increased risk of disturbances in neurotransmission, leading to dysregulation in brain function. Therefore, understanding the regulatory function of vitamin C in antioxidant defence and identification of its molecular targets deserves more attention. One of the key signalling ions is calcium and a transient rise in its concentration is crucial for all neuronal processes. Extracellular Ca2+ influx (through specific ion channels) or Ca2+ release from intracellular stores (endoplasmic reticulum, mitochondria) are precisely controlled. Ca2+ regulates the functioning of the CNS, including growth, development, myelin formation, synthesis of catecholamines, modulation of neurotransmission and antioxidant protection. A growing body of evidence indicates a unique role for vitamin C in these processes. In this short review, we focus on vitamin C in the regulation of calcium-involved pathways under physiological and stress conditions in the brain

Vitamin C Modes of Action in Calcium-Involved Signaling in the Brain

Vitamin C (ascorbic acid) is well known for its potent antioxidant properties, as it can neutralize ROS and free radicals, thereby protecting cellular elements from oxidative stress. It predominantly exists as an ascorbate anion and after oxidation to dehydroascorbic acid and further breakdown, is removed from the cells. In nervous tissue, a progressive decrease in vitamin C level or its prolonged deficiency have been associated with an increased risk of disturbances in neurotransmission, leading to dysregulation in brain function. Therefore, understanding the regulatory function of vitamin C in antioxidant defence and identification of its molecular targets deserves more attention. One of the key signalling ions is calcium and a transient rise in its concentration is crucial for all neuronal processes. Extracellular Ca2+ influx (through specific ion channels) or Ca2+ release from intracellular stores (endoplasmic reticulum, mitochondria) are precisely controlled. Ca2+ regulates the functioning of the CNS, including growth, development, myelin formation, synthesis of catecholamines, modulation of neurotransmission and antioxidant protection. A growing body of evidence indicates a unique role for vitamin C in these processes. In this short review, we focus on vitamin C in the regulation of calcium-involved pathways under physiological and stress conditions in the brain

The Role of MEF2 Transcription Factor Family in Neuronal Survival and Degeneration

The family of myocyte enhancer factor 2 (MEF2) transcription factors comprises four highly conserved members that play an important role in the nervous system. They appear in precisely defined time frames in the developing brain to turn on and turn off genes affecting growth, pruning and survival of neurons. MEF2s are known to dictate neuronal development, synaptic plasticity and restrict the number of synapses in the hippocampus, thus affecting learning and memory formation. In primary neurons, negative regulation of MEF2 activity by external stimuli or stress conditions is known to induce apoptosis, albeit the pro or antiapoptotic action of MEF2 depends on the neuronal maturation stage. By contrast, enhancement of MEF2 transcriptional activity protects neurons from apoptotic death both in vitro and in preclinical models of neurodegenerative diseases. A growing body of evidence places this transcription factor in the center of many neuropathologies associated with age-dependent neuronal dysfunctions or gradual but irreversible neuron loss. In this work, we discuss how the altered function of MEF2s during development and in adulthood affecting neuronal survival may be linked to neuropsychiatric disorders

The Role of MEF2 Transcription Factor Family in Neuronal Survival and Degeneration

The family of myocyte enhancer factor 2 (MEF2) transcription factors comprises four highly conserved members that play an important role in the nervous system. They appear in precisely defined time frames in the developing brain to turn on and turn off genes affecting growth, pruning and survival of neurons. MEF2s are known to dictate neuronal development, synaptic plasticity and restrict the number of synapses in the hippocampus, thus affecting learning and memory formation. In primary neurons, negative regulation of MEF2 activity by external stimuli or stress conditions is known to induce apoptosis, albeit the pro or antiapoptotic action of MEF2 depends on the neuronal maturation stage. By contrast, enhancement of MEF2 transcriptional activity protects neurons from apoptotic death both in vitro and in preclinical models of neurodegenerative diseases. A growing body of evidence places this transcription factor in the center of many neuropathologies associated with age-dependent neuronal dysfunctions or gradual but irreversible neuron loss. In this work, we discuss how the altered function of MEF2s during development and in adulthood affecting neuronal survival may be linked to neuropsychiatric disorders