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Daily News Analysis


12th April, 2024 Health


Source: DownToEarth

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


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.

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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)