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Neuroprotection: VEGF, IL-6, and clusterin: the dark side of the moon
S Pucci1, P Mazzarelli, F Missiroli
1Department of Biopathology, Institute of Anatomic Pathology, University of Rome Tor Vergata, 00133 Rome, Italy. federico.ricci@uniroma2.it
Abstract:
Growth factors and their respective receptors are key regulators in development and homeostasis of the nervous system, and changes in the function, expression, or downstream signaling of growth factors are involved in many neuropathological disorders. Recently, research has yielded a rich harvest of information about molecules and gene, and currently the assumption "a gene-a protein", where each gene encodes the structure of a single protein, is becoming a paradox. In the past years, the discovery of synergic or antagonistic proteins deriving from the same gene is a novelty upsetting. In some way, the conventional function of proteins involved in DNA repair, cell death/growth induction, vascularization, and metabolism is inhibited or shifted toward other pathways by soluble mediators that orchestrate such change depending on the microenvironment conditions. In this chapter, we focus on the antithetic properties that proteins could exert, depending on the microenvironment that orchestrates the complex networks among proteins and their respective partners.
Insights
Growth factors regulate the nervous system, but single genes can produce opposing proteins. The microenvironment dictates protein function, impacting disease and cellular processes like DNA repair and metabolism.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Growth factors and receptors are crucial for nervous system development and function.
- Aberrant growth factor signaling is implicated in neuropathological disorders.
- The traditional
- gene-protein
- paradigm is challenged by single genes producing multiple protein variants.
Purpose of the Study:
- To explore the concept of antithetic protein properties arising from the same gene.
- To understand how microenvironment influences protein function and signaling pathways.
- To highlight the complexity of protein interactions in biological systems.
Main Methods:
- Review of current literature on growth factors, gene expression, and protein interactions.
- Analysis of how microenvironmental factors modulate protein function.
- Discussion of novel findings regarding single-gene protein diversity.
Main Results:
- Proteins can exhibit opposing functions (synergic or antagonistic) depending on the cellular context.
- Soluble mediators orchestrate these functional shifts.
- Conventional protein roles in DNA repair, cell death, vascularization, and metabolism can be altered.
Conclusions:
- The microenvironment plays a critical role in determining protein function and orchestrating complex biological networks.
- Understanding context-dependent protein behavior is essential for comprehending neuropathology.
- The discovery of antithetic protein properties from single genes offers new insights into molecular regulation.
