C. elegans MANF Homolog Is Necessary for the Protection of Dopaminergic Neurons and ER Unfolded Protein Response

Frontiers in Neuroscience
Cory RichmanBhagwati P Gupta

Abstract

Neurotrophic factors (NTFs) are important for the development, function, and survival of neurons in the mammalian system. Mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) are two recently identified members of a novel family of NTFs in vertebrates that function to protect dopaminergic neurons. Although these genes are conserved across eukaryotes, their mechanism of neuroprotection is not fully understood. Sequence searches for MANF/CDNF homologs in invertebrates have identified a single ortholog that is most related to MANF. Here we report the in vivo characterization of the MANF gene, manf-1, in the nematode Caenorhabditis elegans. We found that manf-1 mutants have an accelerated, age-dependent decline in the survival of dopaminergic neurons. The animals also show increased endoplasmic reticulum (ER) stress, as revealed by reporter gene expression analysis of hsp-4, an ER chaperone BiP/GRP78 homolog, suggesting that a failure to regulate the ER unfolded protein response (ER-UPR) may be a contributing factor to dopaminergic neurodegeneration. Expression studies of manf-1 revealed that the gene is broadly expressed in a pattern that matches closely with hsp-4. Consistent...Continue Reading

References

Sep 15, 1975·The Journal of Comparative Neurology·J SulstonS Brenner
Jul 1, 1968·Physiological Reviews·R Levi-Montalcini, P U Angeletti
Apr 1, 1995·Current Opinion in Cell Biology·M Barbacid
Jun 10, 2003·Journal of Molecular Neuroscience : MN·Penka PetrovaJohn W Commissiong
Oct 16, 2003·Molecular and Cellular Biology·Ann-Hwee LeeLaurie H Glimcher
Jan 7, 2006·Cell Death and Differentiation·D LindholmL Korhonen
May 8, 2007·FEBS Letters·Min Ni, Amy S Lee
May 18, 2007·Cell Structure and Function·Naomi MizobuchiKazuhiro Nagata
Jan 10, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shusei HamamichiGuy A Caldwell
Jun 20, 2008·Experimental Cell Research·Andria ApostolouShengyun Fang
Jan 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mari PalgiTapio I Heino
Mar 5, 2009·Protein Engineering, Design & Selection : PEDS·Vimal ParkashAdrian Goldman
Jul 31, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Merja H VoutilainenRaimo K Tuominen
Sep 24, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yong-Qiang YuYu-Xian Shen
Mar 11, 2010·FEBS Letters·Jun HosekiKazuhiro Nagata
Nov 5, 2010·The Journal of Biological Chemistry·Maarit HellmanPerttu Permi
Dec 15, 2010·Molecular Neurodegeneration·Peizhou JiangShu-Hui C Yen
May 9, 2012·Developmental Cell·Michal LevinItai Yanai
Jan 28, 2014·Cell Reports·Dominic GrünNikolaus Rajewsky
Apr 24, 2015·Lancet·Lorraine V Kalia, Anthony E Lang
Apr 29, 2015·Gene Expression Patterns : GEP·Vassilis Stratoulias, Tapio I Heino
Jul 22, 2017·Nature Reviews. Neurology·Claudio Hetz, Smita Saxena
Mar 3, 2018·Nature Communications·Meirong BaiDengke K Ma

❮ Previous
Next ❯

Citations

Apr 6, 2019·Cell Transplantation·Henri J Huttunen, Mart Saarma
Oct 18, 2019·Journal of Developmental Biology·Avijit MallickBhagwati P Gupta
Aug 28, 2020·Cell and Tissue Research·Maria Jӓntti, Brandon K Harvey
Jul 22, 2021·Biochemistry. Biokhimii︠a︡·Dmitry V EreminAnton S Tsybko

❮ Previous
Next ❯

Methods Mentioned

BETA
protein folding
transgenic
fluorescence microscopy
glycosylation
Assay

Software Mentioned

BioRad CFX manager
NIH
Zen2 edition
SPELL
ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.