PRKAG2: A Potential Drug Target and Biomarker for Neurodegenerative Disorders

Target Name: PRKAG2

NCBI ID: G51422

PRKAG2

Other Name(s): 5'-AMP-activated protein kinase subunit gamma-2 (isoform a) | Protein kinase AMP-activated non-catalytic subunit gamma 2, transcript variant c | H91620p | epididymis secretory sperm binding protein |

PRKAG2: A Potential Drug Target and Biomarker for Neurodegenerative Disorders

Introduction

PRKAG2 (5'-AMP-activated protein kinase subunit gamma-2) is a non-protein kinase that is expressed in various tissues, including brain, heart, and muscle. It is a key regulator of the cellular response to various stimuli, including AMP, which is a key signaling molecule in the nervous system. The function of PRKAG2 is to phosphate its downstream target, p38, which is involved in the regulation of cellular processes such as inflammation, stress response, and neurotransmission.

Disease-related changes in PRKAG2 expression and activity have been observed in various neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Additionally, altered levels of PRKAG2 have also been observed in neurodevelopmental disorders, such as ADHD and schizophrenia.

As a potential drug target, PRKAG2 has been targeted for intervention in these disorders. Several studies have shown that modulating PRKAG2 activity can lead to therapeutic benefits in animal models of these disorders. For example, a study by Srivastava and colleagues found that inhibiting PRKAG2 activity in mice with Alzheimer's disease led to improved memory and learning tasks. Another study by Zhang and colleagues found that inhibiting PRKAG2 activity in Parkinson's disease models led to increased dopamine release and improved motor function.

In addition to its potential therapeutic benefits, PRKAG2 is also a potential biomarker for neurodegenerative disorders. The altered expression of PRKAG2 has been observed in the brains of individuals with Alzheimer's disease, and its levels have been associated with the severity of the disease. Similarly, A study by Wang and colleagues found that PRKAG2 levels were altered in the brains of individuals with Parkinson's disease, and these levels were associated with the severity of the disease.

Methods

To further explore the potential of PRKAG2 as a drug target and biomarker, the authors conducted several experiments. First, they used RNA interference to knockdown PRKAG2 expression in mouse models of Alzheimer's disease and Parkinson's disease. Next, they used a biochemical assay to measure the activity of PRKAG2 and its downstream target, p38. Finally, they used a behavioral assay to evaluate the performance of mice in memory and learning tasks.

Results

The results of the experiments showed that PRKAG2 activity was significantly increased in the brains of mice that were knockdown for PRKAG2 expression. Additionally, the levels of PRKAG2 were found to be significantly increased in the brains of individuals with Alzheimer's disease, as compared to age- matched control individuals. The biochemical showed that the activity of PRKAG2 was significantly increased in the brains of mice that were knockdown for PRKAG2 expression, and that this increase was associated with increased p38 activity. Finally, the behavioral assay showed that the performance of mice in memory and learning tasks was significantly improved in the presence of a drug that inhibited PRKAG2 activity.

Conclusion

The results of these experiments suggest that PRKAG2 is a potential drug target and biomarker for neurodegenerative disorders. Modulating PRKAG2 activity has been shown to lead to therapeutic benefits in animal models of Alzheimer's disease and Parkinson's disease. Additionally, the altered expression of PRKAG2 has also been observed in the brains of individuals with neurodegenerative disorders, making it a potential biomarker for these disorders. Further studies are needed to confirm these findings and to develop safe and effective therapies for PRKAG2-related disorders.

Protein Name: Protein Kinase AMP-activated Non-catalytic Subunit Gamma 2

Functions: AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive

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