Sci Adv: Domestic universities have made a major breakthrough in the field of Alzheimer's disease! It is expected to help patients regain their cognition.

Alzheimer's disease (AD) is a common developing neurological degenerative disease characterized by a gradual decline in cognitive ability.
despite the global annual cost of research and development in the disease sector of $1 trillion, the current state of research and development of new drugs is still not optimistic.
recently, researchers from Henan University-McAuley University's Center for Biomedical Joint Innovation and Nan kai University published a study in Science Advances that offers new ideas for targeted treatment for Alzheimer's disease.
report says researchers have found an effective method of siRNA brain delivery and developed a sugar-based "triple interaction" of the stable polymerized siRNA nanopedit, Gal-NP@ siRNA, which has been shown in mouse experiments to penetrate the blood-brain barrier effectively, restoring cognitive ability in AD mice without significant side effects.
two main pathological characteristics of AD are β-amyloid protein accumulation leading to the formation of geriatric plaques and tau protein excessive phosphication leading to nerve fiber entanglement.
previous studies have shown that β amyloid protein-related enzyme BACE1 is the most promising target for the treatment of AD, while small interfering RNA (siRNA) shows great hope for AD therapy through the specific silence of BACE1.
question is, how can drugs be delivered safely and efficiently to the brain? The human brain has a complete protection mechanism, can resist the invasion of harmful substances, of which the blood-brain barrier is to prevent drugs to reach the brain "roadblock."
most drugs are not effective because it is difficult to break through this "level".
the study, researchers developed a glyco-based nano-delivery system using a previously reported stabilization of "triple interactions" (charge, hydrogen bonds, hydrophobics).
the system uses the operation of blood sugar-controlled glucose transport protein 1 (Glut1) to promote nanoproteants to break through the blood-brain barrier.
the traditional single-heavy force (charge) stable siRNA nano-drug, this drug has better siRNA wrapping capacity and compression capacity, can form smaller nanoparticles.
Gal-NP-siRNA preparation process and the mechanism by which the drug worked in mouse models To quantify the efficiency of the siRNA silent BACE1 gene, the researchers treated neuroma cells (Neuro-2a cells) in mice using Gal-NP-siRNA and found that the BACE1 gene was sufficiently silent in Neuro-2a cells, with BACE1 mRNA and proteins reduced by about 46% and 45%, respectively.
Gal-NP-siRNA's effect on the expression levels of BACE1 mRNA (F) and protein (G) pharmacodynamics showed that after 1 hour of infusion of Gal-NP-siRNA, the accumulation of siRNA in the mouse brain peaked and siRNA remained in the mouse brain for 24 hours.
time-imaging of Gal-NP-Cy5-siRNA assessed by fluorescence imaging after a single dose injection, the key question is, of course, how effective is this drug in treating AD? The researchers used a genetically modified mouse commonly used in AD studies to inject nanodrations every three days through an end vein.
behavior tests showed significant improvement in cognitive abilities in mice.
analysis of brain tissue in mice, the researchers found that the hippocupta and cortical BACE1 protein levels decreased significantly in mice and the pathological characteristics of AD decreased significantly.
, the study led to an effective Alzheimer's treatment targeting BACE1.
, the paper concludes by noting that this approach not only promises to treat Alzheimer's disease, but also expands targeted gene therapy for other brain diseases such as Parkinson's disease and glioma.
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