Re: AD Use Case - about ADDLs [science] (corrected an error)

oops. Move "What I don't know:" to below "ADDL complex has_part..."
Corrected message below

-Alan


On Jan 21, 2007, at 9:26 PM, Eric Neumann wrote:

> Bill,
>
> I'm trying to understand the central issue here: is it that ADDL is  
> not a full gene product so one cannot use the Entrez URI?
>

I'm trying to understand this stuff too. Here's my current  
understanding:

APP gene (for which there is an entrez gene entry)-> precursor  
protein (~700AA). Two proteases can cleave it into different  
fragments from 39-42 amino acids. These are collectively called  
Amyloid beta proteins. I.e. Amyloid beta is a protein family, though  
in different contexts it might refer to a specific member of that  
family.

ADDLs are short oligomers of amyloid beta proteins. I've seen it said  
that they are made of Abeta(1-42)  (i.e. the 42 AA cleavage product)


> If so, why not just define the necessary set of peptides as new  
> URI's (in HCLS's namespace for now), with predicate ':derived_from   
> A-beta*56' ?
>

Abeta*56 is also a protein complex of Amyloid beta proteins. 56 here  
refers to the molecular weight in kDa. It wasn't specifically stated  
but it looks to me that Abeta*56 fits the definition of an ADDL. A  
single Abeta1-42 is about 4.5kDa,

The variables are therefore a) which Abeta b) what size complex.

So the relation is more like:

precursor protein_gene_product_of APP
Abeta derived_from precursor (in the BFO sense)
ADDL complex has_part only Abeta (also some sort of cardinality  
specification)

What I don't know:

Whether APP splice form matters. How mutation matters. Whether ADDL  
refers specifically to Abeta1-42 complexes.
What the comment about Abeta1-40 in the immunogen(epitope) field of  
the ADDL antibody in Alzforum means.
Bill's note suggests that shorter fragments of Abeta might be  
consituents of ADDLs. I don't know if these are just experimental  
constructs or whether they occur in vivo.
Whether ADDLs are always composed of multiples of a single form of  
abeta, or whether different species can be mixed.

-Alan

http://en.wikipedia.org/wiki/Amyloid_precursor_protein
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? 
db=PubMed&cmd=Retrieve&dopt=Citation&list_uids=16541076
http://www.pnas.org/cgi/content/full/95/11/6448
http://www.jbc.org/cgi/content/abstract/271/34/20631

Received on Monday, 22 January 2007 04:20:25 UTC