RGD Reference Report - Autophagy, and BiP level decrease are early key events in retrograde degeneration of motoneurons. - Rat Genome Database

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Autophagy, and BiP level decrease are early key events in retrograde degeneration of motoneurons.

Authors: Penas, C  Font-Nieves, M  Fores, J  Petegnief, V  Planas, A  Navarro, X  Casas, C 
Citation: Penas C, etal., Cell Death Differ. 2011 Oct;18(10):1617-27. doi: 10.1038/cdd.2011.24. Epub 2011 Mar 25.
RGD ID: 5685686
Pubmed: PMID:21436843   (View Abstract at PubMed)
PMCID: PMC3172115   (View Article at PubMed Central)
DOI: DOI:10.1038/cdd.2011.24   (Journal Full-text)

Disconnection of the axon from the soma of spinal motoneurons (MNs) leads either to a retrograde degenerative process or to a regenerative reaction, depending on the severity and the proximity to the soma of the axonal lesion. The endoplasmic reticulum (ER) is a continuous membranous network that extends from the nucleus to the entire cytoplasm of the neuronal soma, axon and dendrites. We investigated whether axonal injury is sensed by the ER and triggers the activation of protective mechanisms, such as the unfolded protein response (UPR) and autophagy. We found early (at 3 days) accumulation of beclin1, LC3II and Lamp-1, hallmarks of autophagy, in both degenerating MNs after spinal root avulsion and in non-degenerating MNs after distal nerve section, although Lamp-1 disappeared by 5 days only in the former. In contrast, only degenerating MNs presented early activation of IRE1alpha, revealed by an increase of the spliced isoform of Xbp1 and accumulation of ATF4 in their nucleus, two branches of the UPR, and late BiP downregulation in association with cytoskeletal and organelle disorganization. We conclude that BiP decrease is a signature of the degenerating process, as its overexpression led to an increase in MN survival after root avulsion. Besides, Bcl2 is strongly implicated in the survival pathway activated by BiP overexpression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Nerve Degeneration  ISOBecn1 (Rattus norvegicus)5685686; 5685686protein:increased expression:lumbar spinal cord ventral horn RGD 
Nerve Degeneration  IEP 5685686; 5685686protein:increased expression:lumbar spinal cord ventral horn RGD 
Nerve Degeneration  ISOHspa5 (Rattus norvegicus)5685686; 5685686protein:decreased expression:spinal cordRGD 
Nerve Degeneration  IEP 5685686protein:decreased expression:spinal cordRGD 
Nerve Degeneration  ISOMap1lc3a (Rattus norvegicus)5685686; 5685686protein:increased expression:lumbar spinal cord ventral horn RGD 

Objects Annotated

Genes (Rattus norvegicus)
Becn1  (beclin 1)
Hspa5  (heat shock protein family A (Hsp70) member 5)
Map1lc3a  (microtubule-associated protein 1 light chain 3 alpha)

Genes (Mus musculus)
Becn1  (beclin 1, autophagy related)
Hspa5  (heat shock protein 5)
Map1lc3a  (microtubule-associated protein 1 light chain 3 alpha)

Genes (Homo sapiens)
BECN1  (beclin 1)
HSPA5  (heat shock protein family A (Hsp70) member 5)
MAP1LC3A  (microtubule associated protein 1 light chain 3 alpha)


Additional Information