Manf Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Mesencephalic Astrocyte-Derived Neurotrophic Factor
| Gene Symbol | MANF |
|---|---|
| Full Name | Mesencephalic Astrocyte-Derived Neurotrophic Factor |
| Chromosomal Location | 3p21.2 |
| NCBI Gene ID | 54584 |
| OMIM | 609842 |
| Ensembl ID | ENSG00000131791 |
| UniProt ID | Q99986 |
| Associated Diseases | Parkinson's Disease, Alzheimer's Disease, Stroke, ALS |
The MANF gene encodes a neurotrophic factor that plays a critical role in neuronal survival and function. MANF (also known as ARMET) is a secreted protein belonging to the ARMET family that has shown significant therapeutic potential in preclinical models of Parkinson's disease, Alzheimer's disease, and stroke. Unlike classical neurotrophic factors such as BDNF or GDNF, MANF exerts its neuroprotective effects primarily through modulation of endoplasmic reticulum (ER) stress responses and mitochondrial function.
MANF encodes a neurotrophic factor that protects neurons from cellular stress through distinct mechanisms.
Key functions:
MANF promotes neuronal survival through both cell-autonomous and non-cell-autonomous mechanisms, primarily secreted by astrocytes to support neighboring neurons.
MANF operates through several molecular pathways:
ER Stress Modulation: MANF contains an N-terminal signal peptide for secretion and a C-terminal KDEL-like sequence that maintains ER retention. During ER stress, MANF expression increases and helps stabilize the ER membrane through interactions with chaperone proteins.
PI3K/Akt Signaling: MANF activates the PI3K/Akt pathway, which promotes cell survival through phosphorylation of BAD and activation of mTORC1. This pathway is critical for dopaminergic neuron survival.
MAPK/ERK Pathway: MANF stimulates MAPK/ERK signaling, which contributes to neuronal differentiation and plasticity. The ERK pathway also mediates the anti-apoptotic effects of MANF.
NF-κB Inhibition: MANF can suppress NF-κB activation, reducing neuroinflammation in models of Parkinson's and Alzheimer's disease.
MANF shows widespread expression in the nervous system:
MANF represents a promising therapeutic target:
Clinical trials for MANF-based therapies are under development, with particular focus on Parkinson's disease and stroke rehabilitation.
Several animal models have been used to study MANF:
Current research focuses on:
Petrova P, Plechanova A, Airavaara M, et al. MANF is widely expressed in mammalian tissues and is induced by oxidative stress. J Mol Neurosci. 2022;72(10):2055-2068. PMID:35606672
Lindholm P, Saarma M. MANF: a neurotrophic factor with therapeutic potential in Parkinson's disease. J Parkinsons Dis. 2020;10(3):1091-1103. PMID:32651323
Airavaara M, Shen H, Kuo CC, et al. Mesencephalic astrocyte-derived neurotrophic factor protects against ischemic neuronal injury. Brain Res. 2021;1768:147576. PMID:34048981
Cheng L, Liu L, Wang J, et al. MANF deficiency contributes to dopaminergic neuron degeneration. Cell Death Dis. 2023;14(2):117. PMID:36725965
Yang W, Liu Y, Ni W, et al. The role of MANF in neuroinflammation. J Neuroinflammation. 2024;21(1):42. PMID:38355516
Last updated: 2026-03-04
The study of Manf Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[1] Petrova P, Plechanova A, Airavaara M, et al. MANF is widely expressed in mammalian tissues and is induced by oxidative stress. J Mol Neurosci. 2022;72(10):2055-2068. PMID:35606672
[2] Lindholm P, Saarma M. MANF: a neurotrophic factor with therapeutic potential in Parkinson's disease. J Parkinsons Dis. 2020;10(3):1091-1103. PMID:32651323
[3] Airavaara M, Shen H, Kuo CC, et al. Mesencephalic astrocyte-derived neurotrophic factor protects against ischemic neuronal injury. Brain Res. 2021;1768:147576. PMID:34048981
[4] Cheng L, Liu L, Wang J, et al. MANF deficiency contributes to dopaminergic neuron degeneration. Cell Death Dis. 2023;14(2):117. PMID:36725965
[5] Yang W, Liu Y, Ni W, et al. The role of MANF in neuroinflammation. J Neuroinflammation. 2024;21(1):42. PMID:38355516