ACTH (4-10) Peptide

In acute neurological injuries such as ischemic stroke and traumatic brain injury, neurons may undergo apoptosis due to factors such as hypoxia and ischemia. Research has shown that ACTH (4-10) can significantly inhibit neuronal apoptosis induced by oxygen glucose deprivation (OGD) in vitro cell models, and its mechanism is related to upregulating the expression of anti apoptotic protein Bcl-2 and downregulating the expression of pro apoptotic protein Bax. In the rat model of middle cerebral artery occlusion (MCAO), ACTH (4-10) was administered via lateral ventricle injection. The results showed that the neurological deficit score of the treated group was significantly lower than that of the control group 72 hours after ischemia-reperfusion, and the infarct volume was reduced by about 40%; Pathological sections showed a decrease in the apoptosis rate of hippocampal CA1 neurons in the treatment group. This indicates that ACTH (4-10) can alleviate the degree of nerve damage by inhibiting neuronal apoptosis, providing a potential drug target for the treatment of acute nerve injury.

Neuroinflammation plays an important role in the occurrence and development of nerve damage and neurodegenerative diseases. ACTH (4-10) can reduce the level of reactive oxygen species (ROS) in damaged neurons and enhance the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase; Simultaneously inhibiting the activation of the nuclear factor kappa B (NF - κ B) pathway, reducing the release of pro-inflammatory factors such as tumor necrosis factor alpha (TNF - α) and interleukin-6 (IL-6), and alleviating neuroinflammatory damage. In Parkinson's disease model mice, ACTH (4-10) has a protective effect on dopaminergic neurons in the substantia nigra, which can alleviate motor dysfunction. Its mechanism may be related to reducing inflammatory response. By inhibiting inflammatory responses, ACTH (4-10) can create a relatively favorable microenvironment for neurons, promoting their survival and repair.

After binding to MC3R/MC4R on the surface of neurons, ACTH (4-10) Peptide activates the adenylate cyclase (AC) - cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) signaling pathway, promotes transcription factor CREB phosphorylation, and upregulates the expression of brain-derived neurotrophic factor (BDNF). BDNF can promote neuronal survival, synaptic growth, and maintain plasticity, playing a key role in the repair of damaged nerves. In Alzheimer's disease model mice, ACTH (4-10) was injected intraperitoneally for 4 consecutive weeks. Through water maze experiments, it was found that the escape latency of the treated group mice was shortened by 35%, and the target quadrant dwell time was prolonged by 2 times; Biochemical tests showed a decrease in A β deposition in the mouse brain, a decrease in tau protein hyperphosphorylation levels, and an upregulation of synaptophysin expression. This indicates that ACTH (4-10) can promote the expression of BDNF, enhance synaptic transmission efficiency, promote the expression of neurotrophic factors, delay cognitive decline, and provide new ideas for the treatment of neurodegenerative diseases.

Synaptic plasticity is the foundation of learning and memory in the nervous system, including changes in synaptic transmission efficiency and remodeling of synaptic structures. ACTH (4-10) can affect synaptic plasticity by regulating related signaling pathways and gene expression. As mentioned earlier, it upregulates the expression of BDNF by activating the AC cAMP PKA signaling pathway, promoting synaptic growth and maintaining plasticity. In addition, studies have found that ACTH (4-10) can affect the expression and function of neurotransmitter receptors, further regulating synaptic transmission efficiency and thus having a significant impact on neural plasticity.

Neurogenesis refers to the process of neural stem cell proliferation, differentiation into new neurons, and integration into existing neural networks, which is of great significance in the development and repair of the nervous system. ACTH (4-10) may promote neurogenesis by regulating the expression of neurogenic signaling pathways and growth factors. For example, it can promote the differentiation of neural stem cells into neurons, increase the number of newly generated neurons, and provide a new source of cells for the repair and functional reconstruction of the nervous system.

In the central nervous system, excitatory neurotransmitters such as dopamine and acetylcholine play an important role in the transmission of neural signals and the regulation of neural function. ACTH (4-10) can promote the release of these excitatory neurotransmitters, while inhibiting the excessive inhibitory effect of gamma aminobutyric acid (GABA), improving the signaling efficiency of neural circuits, and thereby enhancing cognitive and emotional regulation functions. For example, in animal experiments, after administering ACTH (4-10), the levels of dopamine and acetylcholine in the animal brain increased, and their learning and memory abilities as well as emotional states improved.

ACTH (4-10) can also regulate the expression and function of neurotransmitter receptors, affecting the binding of neurotransmitters and receptors, thereby regulating the transmission of neural signals. For example, it may alter the sensitivity of neurons to neurotransmitters by upregulating or downregulating the expression levels of certain neurotransmitter receptors, thereby regulating the excitability and inhibitory balance of the nervous system, and having an important impact on the maintenance of normal nervous system function and the occurrence and development of diseases.

By utilizing the neuroprotective and neuroregulatory effects of ACTH (4-10), animal models that are closer to human neurodegenerative diseases can be constructed. For example, by administering animal ACTH (4-10) related treatments to simulate neuronal damage and pathological changes in diseases such as Alzheimer's disease and Parkinson's disease, a more effective model can be provided for studying the pathogenesis and treatment methods of these diseases. In these models, the impact of ACTH (4-10) on disease progression can be further studied, exploring its potential as a therapeutic drug.

Based on the neuroprotective and cognitive function improving effects of ACTH (4-10), it can be chemically modified to develop peptide drugs with better stability and efficacy. For example, by modifying the amino acid residues of ACTH (4-10) through methylation, PEGylation, lipidation, etc., its stability can be improved, its half-life in vivo can be prolonged, and its targeting can be enhanced, solving the problem of natural peptides being easily hydrolyzed by enzymes and cleared quickly in vivo. If the N-terminal methionine of ACTH (4-10) Peptide is methylated and a palmitoyl group is attached to the C-terminal, the half-life of the modified peptide in rats is extended from 0.5 hours of the natural peptide to 3 hours, and the blood-brain barrier penetration rate is increased to 65%. In chronic stress depression model mice, the modified peptide can significantly improve the sugar water preference rate and shorten the forced swimming immobility time of mice, without significant side effects such as weight loss and behavioral abnormalities, demonstrating good clinical translational potential.