MANF Rat

MANF was first identified in 2003 as a secreted protein from mesencephalic astrocytes, a type of glial cell found in the midbrain. It belongs to a family of neurotrophic factors that includes Glial Cell Line-Derived Neurotrophic Factor (GDNF) and Cerebral Dopamine Neurotrophic Factor (CDNF). Structurally, MANF is characterized by its unique ability to be induced by endoplasmic reticulum (ER) stress, which differentiates it from other neurotrophic factors .

MANF plays a crucial role in maintaining cellular homeostasis, particularly under conditions of ER stress. It has been shown to have cytoprotective effects, meaning it can protect cells from various forms of injury. In the context of neurological disorders, MANF has demonstrated the ability to rescue neuronal loss in conditions such as Parkinson’s disease and cerebral ischemia .

One of the key mechanisms through which MANF exerts its effects is by modulating the unfolded protein response (UPR), a cellular stress response related to the ER. By doing so, MANF helps in reducing ER stress and promoting cell survival. Additionally, MANF has been shown to have anti-inflammatory properties, which further contribute to its neuroprotective effects .

The therapeutic potential of MANF has been explored in various preclinical models. For instance, in a rat model of Parkinson’s disease, MANF has been shown to elevate the stimulus-evoked release of dopamine, a neurotransmitter that is deficient in Parkinson’s patients . This suggests that MANF could potentially be used to restore dopaminergic function in such patients.

Moreover, in models of cerebral ischemia, systemic delivery of recombinant MANF has demonstrated promising results. Intranasal and intravenous administration of MANF in rats reduced infarct volume and improved neurological outcomes post-stroke . These findings highlight the potential of MANF as a therapeutic agent for stroke and other neurodegenerative conditions.