Referencia

doi:10.1038/cdd.2011.88

Autores

Natalia Rodríguez-Muela, Francisco Germain, Guillermo Mariño, Patrick S Fitze and Patricia Boya.

Resumen

Autophagy is an essential recycling pathway implicated in neurodegeneration either as a pro-survival or a pro-death mechanism. Its role after axonal injury is still uncertain. Axotomy of the optic nerve is a classical model of neurodegeneration. It induces retinal ganglion cell death, a process also occurring in glaucoma and other optic neuropathies. We analyzed autophagy induction and cell survival following optic nerve transection (ONT) in mice. Our results demonstrate activation of autophagy shortly after axotomy with autophagosome formation, upregulation of the autophagy regulator Atg5 and apoptotic death of 50% of the retinal ganglion cells (RGCs) after 5 days. Genetic downregulation of autophagy using knockout mice for Atg4B (another regulator of autophagy) or with specific deletion of Atg5 in retinal ganglion cells, using the Atg5flox/flox mice reduces cell survival after ONT, whereas pharmacological induction of autophagy in vivo increases the number of surviving cells. In conclusion, our data support that autophagy has a cytoprotective role in RGCs after traumatic injury and may provide a new therapeutic strategy to ameliorate retinal diseases.

Descripción

La autofagia es un mecanismo de reciclaje por el cual la célula degrada proteínas y orgánulos enteros. Se ha descrito su implicación en desórdenes neurodegenerativos, desempeñando una función pro-supervivencia y en ocasiones pro-muerte, sin embargo su papel tras una lesión axonal resulta controvertido. La axotomía de nervio óptico constituye una lesión traumática del sistema nervioso central que conduce a la degeneración y muerte de las células ganglionares de la retina, hecho que también tiene lugar en otras alteraciones retinianas de alta prevalencia como el glaucoma. En el presente trabajo hemos demostrado que la autofagia juega un papel citoprotector para estas neuronas ya que su activación farmacológica rescata de la muerte, tanto in vitro como in vivo, mientras que su bloqueo genético exacerba la degeneración. Estos resultados nos llevan a pensar que la activación controlada de la autofagia podría representar una estrategia terapéutica en desórdenes retinianos menos agresivos que cursen con la pérdida de estas neuronas.

Imagen artículo Agosto

REFERENCIA DEL GRUPO E INVESTIGADOR
Natalia Rodríguez-Muela acaba de defender su tesis doctoral realizada en el Laboratorio de Autofagia en Desarrollo y Fisiopatología dirigido por Patricia Boya en el Centro de Investigaciones Biológicas del CSIC en Madrid. En nuestro laboratorio utilizamos modelos celulares y animales para comprender el papel de la autofagia en la fisiología y la patología de los organismos. Nuestro interés se centra en estudiar la autofagia durante el desarrollo y comprender su implicación en procesos esenciales como la proliferación, diferenciación y la muerte celular. Por otro lado queremos entender cómo defectos en autofagia pueden estar implicados situaciones patológicas como el cáncer y las enfermedades neurodegenerativas.

Descárgate este artículo aquí.
Más artículos en la revista SEBBM.

Did you publish an interesting article recently?

Send it through our application form and we will contact you. Age limit: 32.

The selected articles will participate at the Award to the best article of young people of the SEBBM which will be given during SEBBM conference, that will take place at Spain (free registration, travel and accommodation).

More articles of the month

Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer

01-04-2019

Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New...

Read more

p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton

01-03-2019

Planar cell polarity (PCP) and intercellular junctional complexes establish tissue structure and coordinated behaviors across epithelial sheets. In multiciliated ependymal cells, rotational and translational PCP coordinate cilia beating and direct...

Read more

β‐RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice

01-02-2019

Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In...

Read more

Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons

02-01-2019

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, a process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark is the accumulation of...

Read more

Dynamic acetylation of cytosolic phosphoenolpyruvate carboxykinase toggles enzyme activity between gluconeogenic and anaplerotic reactions

01-12-2018

Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is considered a gluconeogenic enzyme; however, its metabolic functions and regulatory mechanisms beyond gluconeogenesis are poorly understood. Here, we describe that dynamic acetylation of PCK1 interconverts...

Read more

The Helicase PIF1 Facilitates Resection overSequences Prone to Forming G4 Structures

02-11-2018

DNA breaks are complex lesions that can be repaired either by non-homologous end joining (NHEJ) or by homologous recombination (HR). The decision between these two routes of DNA repair is...

Read more

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation

01-10-2018

The nuclear membrane acts as a mechanosensor that drives cellular responses following changes in the extracellular environment. Mechanically ventilated lungs are exposed to an abnormally high mechanical load that may...

Read more

Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria

03-09-2018

Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear...

Read more

STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis

01-08-2018

The brain microenvironment imposes a particularly intense selective pressure on metastasis-initiating cells, but successful metastases bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of...

Read more

A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets

02-07-2018

Activation-induced deaminase (AID) initiates antibody diversification in germinal center (GC) B cells through the deamination of cytosines on immunoglobulin genes. AID can also target other regions in the genome, triggering...

Read more

Protector Members