Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) is a neurotrophic factor that has garnered significant attention due to its unique properties and potential therapeutic applications. Initially discovered in a rat mesencephalic type-1 astrocyte cell line, MANF is known for its neuroprotective effects, particularly in the context of neurodegenerative diseases such as Parkinson’s disease and cerebral ischemia .
MANF is an endoplasmic reticulum (ER)-resident protein that can be secreted upon ER stress induction. It is characterized by its two-domain structure, which is atypical compared to other neurotrophic factors . MANF is highly expressed in various tissues, including the central nervous system (CNS) and peripheral tissues with high metabolic and secretory functions . In mice, MANF expression is particularly notable in brain neurons that regulate energy homeostasis and appetite, as well as in hypothalamic nuclei involved in hormone and neuropeptide production .
The neuroprotective effects of MANF are believed to be mediated through its role in regulating the unfolded protein response (UPR), thereby alleviating ER stress . This regulation is crucial for cell survival, particularly in neurons, which are highly susceptible to ER stress. Additionally, MANF has been shown to activate key signaling pathways, including Akt/mTOR and Erk/mTOR, which are essential for neurite outgrowth and neuronal network formation .
MANF’s ability to promote cell survival and neurite outgrowth makes it a promising candidate for therapeutic applications in neurodegenerative diseases. Studies have demonstrated that MANF can rescue neuronal loss in models of Parkinson’s disease and cerebral ischemia . Furthermore, MANF’s role in metabolic function and inflammation has been highlighted, with research showing that MANF deficiency in mice leads to severe growth retardation and diabetes .
Recombinant MANF, particularly from mouse models, is used extensively in research to study its effects and potential therapeutic applications. Recombinant proteins are produced through genetic engineering techniques, where the MANF gene is cloned and expressed in suitable host cells to produce the protein in large quantities. This allows for detailed studies on MANF’s structure, function, and therapeutic potential.