- Peptide (C)EVSKPLAHHIPVEK, corresponding to amino acid residues 91-104 of human MANF (Accession P55145). Mature MANF protein.
- Western blot analysis of mouse brain lysate (lanes 1 and 4), rat brain lysate (lanes 2 and 5) and human recombinant MANF protein (lanes 3 and 6):1-3. Anti-MANF/ARMET Antibody (#ANT-028), (1:200).
4-6. Anti-MANF/ARMET Antibody, preincubated with MANF/ARMET Blocking Peptide (#BLP-NT028).
- Expression of MANF in rat parietal cortexImmunohistochemical staining of perfusion-fixed frozen rat brain sections using Anti-MANF/ARMET Antibody (#ANT-028), (1:600), followed by goat anti-rabbit-AlexaFluor-488 secondary antibody. Sections derived from parietal cortex of a rat at postnatal day 22 reveal MANF staining (green) in nuclei and cytoplasm of several cells (arrows) in deep layers of the cortex. Nuclei are stained with DAPI (blue).
- Glembotski, C.C. (2011) J. Mol. Cell. Cardiol. 51, 512.
- Lindholm, P. and Saarma, M. (2010) Dev. Neurobiol. 70, 360.
- Parkash, V. et al. (2009) Protein Eng. Des. Sel. 22, 233.
- Airavaara, M. et al. (2012) Parkinsonism Relat. Disord. 18, S143.
- Lindholm, P. et al. (2008) Mol. Cell. Neurosci. 39, 356.
- Allen, S.J. et al. (2013) Pharmacol. Ther. 138, 155.
- Wang, H. et al. (2014) PLoS One 9, e90433.
The novel protein mesencephalic astrocyte-derived neurotrophic factor (MANF) is a survival molecule (alternatively referred to as arginine-rich, mutated in early stage tumors, or ARMET) that has high selectivity for dopaminergic neurons of the midbrain1,2. There, it induces proliferative and protective effects against neurodegeneration (usually caused by 6-hydroxydopamine); its therapeutic potential in dopamine-related neurodegenerative disorders such as Parkinson's disease is therefore promising3,4.
MANF is also expressed cardiac tissues. As was recently suggested, it induces cardioprotection in the heart and anti-hypertrophic effects via reducing endoplasmic reticulum stress in ischemic conditions in both the heart and the brain. Thus, its effects stretch beyond rescue and protection of dopaminergic neurons alone1,5.
Generally, neurotrophic factors (NTFs) provide support, protection, and regulation for neurons – with each group of neurons having their own unique NTFs – both during development and at adulthood. Other noticeable NTFs include neurotrophin-3 and -4 (NT3 and NT4), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and glial cell derived neurotrophic factor (GDNF)6.
MANF is considered to be evolutionary conserved within Mammalia and beyond (including distant species such as nematode and fruit fly – the latter shares more than 50% identity with human MANF gene) and is highly mutative in many tumors. It is mostly composed of alpha helices and random coils; its structure essentially differs from any other neurotrophic factor. It is suggested that the protein initiates intracellular signaling cascade by binding to cell-surface lipids and membranes via its cysteine-rich N-terminal. Together with its C-terminal which contains a disulfide bridge that endows a cytoprotective response against ER stress, MANF is implied to be bi-functional3,7.
Species reactivity key:
Anti-MANF/ARMET Antibody (#ANT-028) is a highly specific antibody directed against an epitope of the human protein. The antibody can be used in western blot and immunohistochemistry applications. It has been designed to recognize MANF from human, rat and mouse samples.