Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF): An Emerging Therapeutic Target for Neurodegenerative Disorders

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a member of the new family of neurotrophic factors (NTFs) with a unique structure and functions compared to other conventionally known NTFs. MANF is broadly expressed in developing and mature tissues, including the central nervous system and peripheral nervous system tissues. Growing research demonstrated that MANF protects neurons from endoplasmic reticulum (ER) stress-associated complications by restoring ER homeostasis and regulating unfolded protein response. This review discusses MANF signaling in neurodegenerative conditions with specific emphasis given to its overall effect and mechanisms of action in experimental models of Parkinson's disease, Alzheimer's disease, and stroke. Additional perspectives on its potential unexplored roles in other neurodegenerative conditions are also given.

Automated summary

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a unique member of the neurotrophic factors (NTFs) family, with distinct structure and functions. It is widely expressed in developing and mature tissues, including the central and peripheral nervous system tissues. Research has shown that MANF protects neurons from complications associated with endoplasmic reticulum (ER) stress by restoring ER homeostasis and regulating unfolded protein response. This review focuses on MANF signaling in neurodegenerative conditions, particularly in experimental models of Parkinson's disease, Alzheimer's disease, and stroke, and also discusses its potential roles in other neurodegenerative conditions.