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Amyloid Receptor and Inhibitor for AD Pathology_Seoul National Univ.
Korea Health Industry Development Institute (KHIDI) South Korea flag South Korea
Abstract ID:
Amyloid receptor and inhibitor for AD pathology...
Contact Yong U Kim
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1. Background of Technology

1.1. Amyloid hypothesis in Alzheimer's disease

- Clinical association of amyloid42 oligomers with Alzheimer's disease

: Detection of amyloid42 oligomers in the brain of AD patients

: Apparent evidence for the role of amyloid42 oligomer in AD Pathology

           : High ratio of Amyloid 42/40 for pathology


1.2. Amyloid42 receptors: not successful yet

- RAGE (Nature 1996)

          : Role in amyloid transport in BBB (2008, 2009, ICAD)

          : However, a role in the memory impairment of AD is not clear

- ABAD (Science 2005)

          : Role in mitochondria for amyloid toxicity

          : However, a role of ABAD in the memory impairment of AD is not clear

-Prion (Nature 2009) etc.

          : Role in LPT

          : However, a role in the memory impairment of AD is not clear yet.


1.3. Limited available targets in the amyloid pathology for drug development in AD

- Beta, gamma secretases are good targets but development of inhibitors have problems.

          : Gamma-secretase: too many substrates  

: Beta secretase: Difficulty to design inhibitor in brain

-Aggregation blockers, amyloid antibody etc

          : Long history, being tried by many groups.


1,4.  Looking for New therapeutic targets

 -Additional new targets are needed.


2. Description on Technology Applied

2.1. Amyloid 42-binding receptor (AIMP) discovered

-Interaction was confirmed in in vitro and cell level

-Amyloid42-selective interaction (Amyloid40 not bound))

-Monomer and oligomeric forms of amyloid42 bind to AIMP receptor

-Binding region was identified by in silico modeling and by mutagenesis

2.2. Role of the amyloid receptor in amyloid pathogenesis

-Increased expression of AIMP in the brains of AD and APP moce

-Essential role of AIMP receptor in neurotoxicity and Tau phosphorylation in cultured neuronal cells

-Inhibition of amyloid42-induced memory impairment in AIMP receptor KO mice (icv injection)

-No reduction in amyloid42-induced LTP in the brain of AIMP receptor KO mice.

-AIMP KO/PDAPP double transgenic mice rescue memory impairment of PDAPP mice.

-There is another ligand for the receptor and thus, selective inhibition is required to avoid unwanted effects.


2.3. Small compound inhibitor (inhibitor X) against amyloid receptor:

-AIMP inhibitor compound Isolated from in silico modeling

          : Using in silico-modeling of the receptor and amyoid42, one million compounds were screened.

- In vitro, in vivo effects: Inhibition of receptor-mediated memory impairments

          : AIMP inhibitor inhibits the interaction of amyloid42 with AIMP

          : AIMP inhibitor inhibits amyloid42-induced neuronal toxicity in vitro

          : AIMP inhibitor inhibits amyloid42-induced memory impairment (memory test after amyloid42 i.c.v. injection).

          : AIMP plays a role in neuronal transport of amyloid42

          : Being tested for BBB transport.


Taken together, these in vitro and  in vivo analysis of AIMP and its inhibitor provide a proof of concept that AIMP may serve as a receptor of amyloid42 (Fig. 1)

Type of Business Relationship Sought
US9234038B2, US8124358B2, EP2268296B1, PCT/KR2008/006570
Last Updated Jun 2016
Technology Type THERAPEUTIC
Phase of Development EARLY STAGE