CISD1: A Potential Drug Target for Neurological Disorders (G55847)

Target Name: CISD1

NCBI ID: G55847

CISD1: A Potential Drug Target for Neurological Disorders

CISD1, also known as MitoNEET, is a protein that is expressed in the brain and plays a crucial role in the development and maintenance of neural stem cells. It is a key regulator of the microtubule network, which is a vital structure that transports vesicles and organelles within cells.

Recent studies have identified CISD1 as a potential drug target for various neurological and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia. This is because the disruption of microtubule dynamics has been implicated in the pathophysiology of these disorders.

One of the key reasons for the potential of CISD1 as a drug target is its role in the regulation of neuronal excitability. The microtubule network plays a critical role in the transmission of neural signals, and CISD1 is involved in the regulation of the speed at which these signals are transmitted.

Disruptions in microtubule dynamics, such as those caused by CISD1, have been linked to increased neuronal excitability, which can lead to the development of neurodegenerative disorders. This is because increased neuronal excitability can cause the cells to undergo an abnormal transition, leading to the loss of normal cellular structure and function.

In addition to its role in neuronal excitability, CISD1 has also been shown to play a key role in the regulation of synaptic plasticity, which is the ability of the brain to learn and adapt over time. The microtubule network is involved in the regulation of synaptic plasticity, and CISD1 plays a critical role in the formation and maintenance of microtubules.

This is why CISD1 is such an attractive drug target, as potential therapeutic interventions that target this protein have the potential to restore normal cellular function and protect against the development of neurodegenerative disorders.

In conclusion, CISD1 is a protein that plays a crucial role in the development and maintenance of neural stem cells, and it is a potential drug target for various neurological and psychiatric disorders. Further research is needed to fully understand the role of CISD1 in the regulation of neural function and the development of neurodegenerative disorders.

Protein Name: CDGSH Iron Sulfur Domain 1

Functions: L-cysteine transaminase that catalyzes the reversible transfer of the amino group from L-cysteine to the alpha-keto acid 2-oxoglutarate to respectively form 2-oxo-3-sulfanylpropanoate and L-glutamate (PubMed:36194135). The catalytic cycle occurs in the presence of pyridoxal 5'-phosphate (PLP) cofactor that facilitates transamination by initially forming an internal aldimine with the epsilon-amino group of active site Lys-55 residue on the enzyme (PLP-enzyme aldimine), subsequently displaced by formation of an external aldimine with the substrate amino group (PLP-L-cysteine aldimine). The external aldimine is further deprotonated to form a carbanion intermediate, which in the presence of 2-oxoglutarate regenerates PLP yielding final products 2-oxo-3-sulfanylpropanoate and L-glutamate. The proton transfer in carbanion intermediate is suggested to be controlled by the active site lysine residue, whereas PLP stabilizes carbanion structure through electron delocalization, also known as the electron sink effect (PubMed:36194135). Plays a key role in regulating maximal capacity for electron transport and oxidative phosphorylation (By similarity). May be involved in iron-sulfur cluster shuttling and/or in redox reactions. Can transfer the [2Fe-2S] cluster to an apo-acceptor protein only when in the oxidation state, likely serving as a redox sensor that regulates mitochondrial iron-sulfur cluster assembly and iron trafficking upon oxidative stress (PubMed:21788481, PubMed:23758282, PubMed:17584744)

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