Acetylcholinesterase-derived peptides and uses thereof

Abstract

The invention relates to a cell growth and/or differentiation regulatory peptide comprising a sequence of about 9 to about 150 amino acids derived from acetylcholinesterase amino acid sequence, preferably from the C-terminal region of acetylcholinesterase. The invention also relates to pharmaceutical compositions comprising the peptides, particularly for use in promoting survival of stem cells, promoting differentiation of stem cells, promoting growth of stem cells and/or promoting the growth-enhancing effect of a growth factor on stem cells, alone, or in combination with other growth factors. Of particular interest is the use of the peptides in the treatment of thrombocytopenia, post-irradiation conditions, post-chemotherapy conditions, or conditions following massive blood loss and promotion of neural progenitors in use for cell therapies aimed at restoring neural functions in diseased individuals. Further, the invention relates to antibodies against the peptides, inter alia for diagnostic use, for example, the diagnosis of stress-induced male infertility. The invention also relates to in vitro and in vivo methods for screening of drugs that affect the central nervous system, and are potential modulators of interactions between the “readthrough” form of acetylcholinesterase, AChE-R, the intracellular receptor RACK1 and the kinase PKC.

1 . An antibody directed against the ARP peptide as denoted by SEQ ID NO:1, which antibody is specific for any one of the AChE-R variant of acetylcholinesterase and a C-terminal peptide derived there from.  
     
     
         2 . The antibody according to  claim 2 , for use in the diagnosis of stress-induced male infertility.  
     
     
         3 . A method for the diagnosis of stress-induced male infertility comprising obtaining a sperm cell sample from said male; smearing and drying said sample; contacting said dried sample with an antibody specific for the AChE-R variant of acetylcholinesterase; removing unbound antibody; detecting the extent of reaction between said antibody and the AChE-R variant of acetylcholinesterase or a fragment thereof present in said sample; determining the pattern of expression of the AChE-R variant of acetylcholinesterase or a fragment thereof, in said sperm cells; whereby the absence of AChE-R from sperm heads together with intense presence in the midpiece region indicates the presence of stress-induced male infertility.  
     
     
         4 . The method according to  claim 3 , for use in fertility counseling.  
     
     
         5 . A kit for the diagnosis of stress-induced male infertility, comprising: 
 (a) an antibody specific for the AChE-R variant;    (b) means for collecting a sperm sample;    (c) slides for smearing the sperm sample;    (d) means for detecting the antibody;    (e) negative control slides.