Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) is a protein that has garnered significant interest due to its neuroprotective properties. It is a member of the neurotrophic factor family, which plays a crucial role in the survival, development, and function of neurons. MANF is unique in its structure and function, distinguishing it from other neurotrophic factors.
MANF is a small, two-domain protein that is primarily localized in the endoplasmic reticulum (ER). It is also secreted in response to ER stress. The protein has a unique dual mode of action: it can function both intracellularly and extracellularly. Intracellularly, MANF helps in maintaining ER homeostasis and protecting cells from ER stress-induced apoptosis. Extracellularly, it promotes the survival of dopaminergic neurons, which are critical in the context of neurodegenerative diseases such as Parkinson’s disease .
The neuroprotective effects of MANF are primarily attributed to its ability to modulate the unfolded protein response (UPR). By regulating UPR, MANF helps in alleviating ER stress, which is a common feature in many neurodegenerative conditions. Additionally, MANF has been shown to enhance GABAergic transmission to dopaminergic neurons, further supporting its role in neuronal survival .
Recombinant MANF, particularly the human form with a His tag, is produced using recombinant DNA technology. The His tag is a sequence of histidine residues added to the protein to facilitate its purification. This recombinant form is used in various research applications to study the protein’s function and therapeutic potential. The His tag allows for easy purification and detection of the protein, making it a valuable tool in biochemical and cell biology studies .
MANF has shown promise in preclinical models of neurodegenerative diseases. Its ability to protect dopaminergic neurons makes it a potential therapeutic candidate for conditions like Parkinson’s disease. Additionally, MANF’s role in modulating ER stress and promoting cell survival suggests that it could be beneficial in other diseases characterized by ER stress, such as diabetes and certain types of cancer .