Neurotrophins

Key Biological Properties: GMF is a 141 amino acid, multifunctional protein highly conserved across species, showing 99% homology between humans and rodents . It is predominantly an intracellular protein localized mainly in astrocytes but also found in some neuronal populations .

Expression Patterns and Tissue Distribution: GMF is primarily expressed in the brain, particularly in astrocytes, but is also present in other tissues such as the colon, thymus, and kidney . It possesses consensus phosphorylation sites and is rapidly phosphorylated in astrocytes upon stimulation .

Primary Biological Functions: GMF plays a crucial role in brain cell differentiation, neural regeneration, and inhibition of tumor cell proliferation . It is involved in the activation of p38 MAP kinase, which is essential for stress-related signal transduction .

Role in Immune Responses and Pathogen Recognition: GMF overexpression in astrocytes promotes the production of cytokines like granulocyte-macrophage colony-stimulating factor (GM-CSF), which activates microglia, the antigen-presenting cells in the nervous system .

Mechanisms with Other Molecules and Cells: GMF interacts with various molecules and cells through phosphorylation and activation of signaling pathways. For instance, PKA-phosphorylated GMF enhances the activity of p38 MAP kinase .

Binding Partners and Downstream Signaling Cascades: GMF overexpression stimulates p38 MAP kinase activity and activates the redox enzyme CuZn superoxide dismutase (CuZnSOD) and transcription factors such as nuclear factor-κB (NF-κB) and cAMP response element binding protein (CREB) . This leads to the induction and secretion of neurotrophins like nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) .

Transcriptional Regulation: GMF expression is regulated at the transcriptional level by various factors, including blood flow and Notch signaling .

Post-Translational Modifications: GMF undergoes phosphorylation, which is crucial for its activation and function . Additionally, GMF interacts with mitochondrial membrane ATPase ATAD3A, influencing mitochondrial function and reactive oxygen species (ROS) production .

Biomedical Research: GMF is a valuable tool in studying neuroinflammation and neurodegeneration. It has been found to be upregulated in several neuroinflammatory and neurodegenerative conditions, making it a potential therapeutic target .

Diagnostic Tools: GMF can serve as a biomarker for various neurological disorders due to its involvement in brain function and immune responses .

Therapeutic Strategies: Targeting GMF may offer new therapeutic approaches for treating neurodegenerative diseases and conditions involving neuroinflammation .

Development: GMF is essential for the development of the nervous system, particularly in neuronal survival and differentiation .

Aging and Disease: GMF plays a role in the aging process and is implicated in various diseases, including neurodegenerative disorders like Alzheimer’s and Parkinson’s . Its involvement in immune activation and stress-related signal transduction makes it a critical factor in maintaining brain health throughout life .