Scientists Discover Potential Barrier Protein Against Alzheimer's
In a groundbreaking discovery, a team of researchers led by Dr. Junmin Peng from St. Jude's Departments of Structural Biology and Developmental Neurobiology has unveiled the defensive role of the protein midkine in slowing the progression of Alzheimer's disease at a molecular level.
The researchers conducted their study using mice engineered to produce higher levels of amyloid beta, mimicking the conditions of Alzheimer's in humans. Some of these mice had the midkine gene removed to assess its impact. The results were striking: mice without midkine developed significantly more amyloid beta plaques than those retaining the gene.
These protein assemblies, or plaques, are known to trigger memory loss and cognitive decline. Alzheimer's disease is a neurodegenerative condition characterised by the accumulation of amyloid beta proteins forming damaging clumps.
The presence of midkine effectively disrupted the assembly of large amyloid structures, as shown by fluorescence experiments using thioflavin T dye. NMR signals diminished as plaques formed, making them hard to analyse, but returned when midkine was added, indicating the protein had broken up these larger assemblies.
Midkine hinders two critical steps in amyloid beta aggregation: elongation and secondary nucleation. This finding suggests that midkine, or drugs that replicate its effect, could stop plaques from forming at all as an alternative to existing therapies.
Most therapeutic strategies for Alzheimer's have targeted these plaques after formation with limited success. The team at St. Jude views this discovery as the beginning of a broader investigation into how this molecule can be used to disrupt disease progression at its source.
Understanding how midkine operates across different systems could help identify shared mechanisms and expand its therapeutic potential. The protein's role in other diseases, including cancer and inflammation, further underscores its biological importance.
Dr. Peng mentioned the potential for designing small molecules that mimic midkine's binding action. Since midkine is naturally produced in the human body, synthetic compounds based on its structure may offer a gentler, more targeted treatment option with fewer adverse effects.
This research is associated with studies on the protein Clusterin, which acts as a molecular chaperone preventing amyloid-beta aggregation. The findings confirm that midkine acts not just in artificial lab conditions but within the living brain, influencing disease progression directly. The study suggests a shift in how Alzheimer's might be approached: by preventing amyloid beta from aggregating in the first place, rather than trying to remove it once the damage is done.
