Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) is a protein that has garnered significant interest in the field of neurobiology due to its unique properties and potential therapeutic applications. Initially derived from a rat mesencephalic type-1 astrocyte cell line, MANF is known for its ability to selectively protect dopaminergic neurons, which are crucial for motor control and are affected in diseases like Parkinson’s .
MANF is an arginine-rich protein that is encoded by the MANF gene. It is localized in the endoplasmic reticulum (ER) and Golgi apparatus, and it is also secreted extracellularly . The protein plays a critical role in promoting the survival of dopaminergic neurons and modulating GABAergic transmission to these neurons . Additionally, MANF inhibits cell proliferation and protects against ER stress-induced cell death .
In the uninjured brain, MANF is predominantly expressed in neurons. However, its expression pattern changes significantly in response to injury. For instance, in ischemic stroke models, MANF expression shifts from neurons to inflammatory cells such as microglia and macrophages . This transition suggests that MANF may play a role in regulating post-stroke inflammation and promoting tissue recovery .
Recombinant human MANF has shown promising results in various experimental models. In a rat model of cortical ischemic stroke, systemic delivery of recombinant MANF reduced infarct volume and improved neurological outcomes . Intranasal and intravenous administration of recombinant MANF also demonstrated anti-inflammatory effects, such as decreasing pro-inflammatory cytokines and increasing anti-inflammatory cytokines like IL-10 .
The therapeutic potential of MANF extends beyond stroke. It has been implicated in various diseases, including diabetes, deafness, developmental delay, and short stature syndrome . The protein’s ability to modulate ER stress and promote cell survival makes it a promising candidate for treating neurodegenerative diseases and other conditions characterized by cellular stress and inflammation.