SUNNYVALE, Calif., Jan. 16, 2013 /PRNewswire/ -- Amarantus BioScience, Inc. (OTCQB: AMBS), a biotechnology company discovering and developing treatments and diagnostics for diseases associated with protein misfolding and apoptosis centered around its patented therapeutic protein Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF), today announced that an independent peer-reviewed research paper entitled Mesencephalic astrocyte-derived neurotrophic factor (MANF) secretion and cell surface binding are modulated by KDEL receptors was published in the Journal of Biological Chemistry. The research paper concludes "These findings provide insight into the mechanisms of MANF neuroprotection, and may be applicable to understanding its functions in other secretory tissues."
The endoplasmic reticulum (ER) is the part of the cell where unfolded proteins are properly folded and then exported into different parts of the cell, or secreted out of the cell, so that they can perform their normal biological functions. When the ER becomes stressed, protein folding is compromised, and cells can become dysfunctional. Apoptosis, also known as Programmed Cell Death, is one of the main side effects of protein misfolding due to ER stress, and several independent peer-reviewed research papers have demonstrated that MANF plays a critical role in reducing protein misfolding and apoptosis. MANF has been shown to be upregulated inside the cell, and subsequently secreted out of the cell, with data demonstrating that MANF ultimately reduces apoptosis in the cells in which it originates, the cells it interacts with once secreted out of the cell, as well as when manufactured MANF is administered to various parts of the body undergoing ER stress. Amarantus is seeking to administer manufactured MANF to areas in the body where ER-stress occurs due to injury or disease, giving the body additional quantities of MANF during times of stress in order to reduce apoptosis and improve cellular function. The Company believes that if cellular function can be improved, overall system recovery is likely in many therapeutic indications. ER-stress and protein misfolding appear to be a key component of Parkinson's disease biology. Amarantus' Chief Scientist originally discovered MANF, and the Company was awarded composition of matter patents on MANF in Europe in 2010 and in the United States in 2011. The Company also recently won a court challenge to its composition of matter patents in Europe. The Company also owns worldwide patent applications covering various methods of using MANF as it relates to neurological conditions.
In this research paper, the authors describe the process by which MANF's intracellular activity (autocrine) may be regulated through MANF binding to the canonical ER-specific retention receptors with the amino acid sequence 'KDEL', known as 'KDELRs' (KDEL Receptors). Researchers expressed, or blocked, a key amino acid sequence on the MANF molecule known as 'RTDL,' which is a highly-conserved amino acid sequence that was shown in this research paper to be required for retention of MANF in the ER, or for secretion of MANF out of the ER, with signal activation through the KDELRs. Further, the research paper goes on to suggest that certain KDELRs are resident on the cell surface membrane, and that MANF's extracellular activity (paracrine) is regulated, at least in part, via cell-surface KDELRs. Interestingly, the paper suggests that following ER stress, there is an increase in expression of KDELRs on the cell surface membrane, opening the possibility that MANF's paracrine activity may be more potent or broad in times of ER stress.