Source: DownToEarth

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Context

• A gene variant could lower chances of developing Alzheimer’s by 70%, could help in design of new treatments: Study.

Details

About the Study

• Objective: Investigating why certain individuals with a high-risk gene variant (APOEε4) for Alzheimer’s disease remain protected from developing the condition.
• Findings:
  • A mutated version of a gene responsible for fibronectin production reduces the risk of developing Alzheimer’s by 71%.
  • This fibronectin variant also delays disease onset by approximately four years in individuals who eventually develop Alzheimer’s.

Role of Fibronectin in Alzheimer’s

• Blood-Brain Barrier (BBB) Function:
  • Fibronectin is a component of the BBB, which regulates the movement of substances into and out of the brain.
  • Maintaining the integrity of the BBB prevents the accumulation of amyloid beta protein in the brain, a hallmark of Alzheimer’s.
• Protective Mechanism: The fibronectin variant identified in the study prevents the build-up of fibronectin, thereby preserving BBB function and facilitating amyloid clearance.

Implications for Treatment

• Potential Therapeutic Target: Drugs that reduce excess fibronectin could offer protection against Alzheimer’s by maintaining BBB integrity and promoting amyloid clearance.
• Drug Development: Identifying compounds that target fibronectin could lead to novel treatments for Alzheimer’s, potentially addressing the disease’s underlying pathology rather than just its symptoms.

About Fibronectin

• It is a high-molecular-weight glycoprotein found in the extracellular matrix and circulating in the blood plasma.
• It plays crucial roles in various biological processes, including cell adhesion, migration, growth, and differentiation.

Structure of Fibronectin:

• Primary Structure:
  • Fibronectin is composed of repeating structural motifs called modules or domains.
  • It is encoded by a gene located on human chromosome 2.
• Domain Structure:
  • Fibronectin contains multiple types of domains, including type I, type II, and type III repeats.
  • These repeats form distinct functional regions within the protein.
• Glycosylation: Fibronectin undergoes post-translational modifications, including glycosylation, which affects its function and stability.
• Alternative Splicing: Fibronectin can be alternatively spliced, resulting in different isoforms with distinct functions.

 

Functions of Fibronectin:

• Cell Adhesion: Fibronectin binds to cell surface receptors such as integrins, facilitating cell adhesion to the extracellular matrix.
• Extracellular Matrix Organization: Fibronectin contributes to the structural organization of the extracellular matrix, providing support and anchorage for cells.
• Cell Signaling: Fibronectin-mediated interactions with cell surface receptors trigger intracellular signaling pathways, regulating various cellular processes.
• Tissue Repair and Remodeling: Fibronectin plays a crucial role in wound healing, tissue regeneration, and remodeling processes.

Roles of Fibronectin in Health and Disease:

• Development and Morphogenesis: Fibronectin is essential for embryonic development, including processes like gastrulation and tissue morphogenesis.
• Wound Healing: Fibronectin facilitates the migration of cells to wound sites and promotes tissue repair by providing a scaffold for cell adhesion and proliferation.
• Cancer Progression and Metastasis: Altered expression and function of fibronectin are associated with cancer progression, invasion, and metastasis.
• Fibrosis: Fibronectin deposition contributes to the development of fibrosis in various organs, including the liver, lung, and kidney.

Research Applications of Fibronectin:

• Cell Culture Substrate: Fibronectin-coated surfaces are commonly used in cell culture experiments to promote cell adhesion and proliferation.
• Tissue Engineering: Fibronectin-based biomaterials are utilized in tissue engineering applications to mimic the natural extracellular matrix and promote tissue regeneration.
• Drug Delivery: Fibronectin-targeting ligands are investigated for their potential use in targeted drug delivery systems, particularly for cancer therapy.
• Disease Biomarker: Altered levels of fibronectin expression or isoform distribution are explored as potential biomarkers for various diseases, including cancer and fibrosis.

Must read article:

Alzheimer’s disease

Sources:

DownToEarth

PRACTICE QUESTION Q.  Discuss the role of genetic variations in shaping individual susceptibility to neurodegenerative disorders. Provide examples from recent research to support your argument. (250 Words)