PAGE TITLE
A new method to alter amyloid precursor protein processing and amyloidogenesis
PAGE SUMMARY
Altered Amyloid Precursor Protein (APP) processing and Aβ production have long been recognized as major factors in the cognitive decline associated with both Alzheimer’s Disease (AD) and HIV-Associated Neurocognitive Disorders (HAND). However, recent studies show that a linear link between β-amyloid seeding and disease progression - as proposed in the original “amyloid cascade hypothesis”- is an over-simplified explanation for these complex disorders. Events leading to APP maturation and processing rely on sophisticated molecular machinery that regulates its trafficking, modification, and cleavage. Therefore, molecular tools able to precisely affect these processes represent a powerful approach to relieve the burden of these devastating disorders.
Building on their initial observations concerning overlapping trafficking behavior of APP and US9 (a Herpes Simplex Virus transport protein), the Meucci lab designed several US9-based molecular tools able to manipulate APP processing by either direct or indirect modalities. Available data show that these US9-based molecular tools are capable of modifying APP trafficking and processing, resulting in reduced APP β-cleavage and amyloidogenic load. Additionally, soluble αAPP fragments with neuroprotective and neurotrophic properties are released from transduced cells. This novel approach, which exploits the molecular properties of a viral protein to achieve specific effector engagement, establishes US9 as a powerful molecular driver for functional neuronal targeting thus paving the way to new therapeutics for pathologies implicating APP misprocessing, like AD and HAND.
APPLICATIONS
TITLE: Applications
Tool for modifying APP processing and Aβ production
Tool for studying contribution of lipid rafts to neurodegenerative disease
Investigate pathological states of Alzheimer’s and HIV-associated neurocognitive disorders
ADVANTAGES
TITLE:Advantages
Unique approach to deliver functional cargo to act as therapy
Target and modulate amyloid precursor protein processing machinery
Approach can be extended to other disorders with altered protein trafficking and accumulation
IP STATUS
Intellectual Property and Development Status
United States Patent Pending- 16/380,719
https://patents.google.com/patent/US20190309026A1/en?oq=16%2f380%2c719
PUBLICATIONS
References
Brandimarti R. et al. The lipid raft-dwelling protein US9 can be manipulated to target APP compartmentalization, APP processing, and neurodegenerative disease pathogenesis. Scientific Reports, 2017, 7, p. 15103.
https://www.nature.com/articles/s41598-017-15128-8
Pedrazzi M. et al. Molecular features contributing to intracellular localization and dynamic behavior of US9 protein of Herpes Simplex Virus I in a virus-free cellular context. PLoS One, 2014, 9(8), e104634.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136771/
Contact Information
Tanvi Muni
Licensing Manager
Drexel University
tm3439@drexel.edu