Neuroprotective Strategy in Retinal Degeneration: Suppressing ER Stress-Induced Cell Death via Inhibition of the mTOR Signal

نویسندگان

  • Bin Fan
  • Ying-Jian Sun
  • Shu-Yan Liu
  • Lin Che
  • Guang-Yu Li
چکیده

The retina is a specialized sensory organ, which is essential for light detection and visual formation in the human eye. Inherited retinal degenerations are a heterogeneous group of eye diseases that can eventually cause permanent vision loss. UPR (unfolded protein response) and ER (endoplasmic reticulum) stress plays an important role in the pathological mechanism of retinal degenerative diseases. mTOR (the mammalian target of rapamycin) kinase, as a signaling hub, controls many cellular processes, covering protein synthesis, RNA translation, ER stress, and apoptosis. Here, the hypothesis that inhibition of mTOR signaling suppresses ER stress-induced cell death in retinal degenerative disorders is discussed. This review surveys knowledge of the influence of mTOR signaling on ER stress arising from misfolded proteins and genetic mutations in retinal degenerative diseases and highlights potential neuroprotective strategies for treatment and therapeutic implications.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Algae Undaria pinnatifida Protects Hypothalamic Neurons against Endoplasmic Reticulum Stress through Akt/mTOR Signaling.

Increased endoplasmic reticulum (ER) stress is known to be one of the causes of hypothalamic neuronal damage, as well as a cause of metabolic disorders such as obesity and diabetes. Recent evidence has suggested that Undaria pinnatifida (UP), an edible brown algae, has antioxidant activity. However, the neuroprotective effect of UP has yet to be examined. In this study, to investigate the neuro...

متن کامل

Modulation of valosin-containing protein by Kyoto University Substances (KUS) as a novel therapeutic strategy for ischemic neuronal diseases

Retinal ischemia causes several vision-threatening diseases, including diabetic retinopathy, retinal artery occlusion, and retinal vein occlusion. Intracellular adenosine triphosphate (ATP) depletion and subsequent induced endoplasmic reticulum (ER) stress are proposed to be the underlying mechanisms of ischemic retinal cell death. Recently, we found that a naphthalene derivative can inhibit AT...

متن کامل

KUS121, a VCP modulator, attenuates ischemic retinal cell death via suppressing endoplasmic reticulum stress

Ischemic neural damages cause several devastating diseases, including brain stroke and ischemic retinopathies, and endoplasmic reticulum (ER) stress has been proposed to be the underlying mechanism of the neuronal cell death of these conditions. We previously synthesized Kyoto University substances (KUSs) as modulators of valosin-containing protein (VCP); KUSs inhibit VCP ATPase activity and pr...

متن کامل

Neuroprotective effects of memantine in a mouse model of retinal degeneration induced by rotenone.

This is the first report of the in vivo effectiveness of memantine as a neuroprotective agent against rotenone-induced retinal toxicity. We tested the hypothesis that uncompetitive NMDAR blockade with memantine prevents mitochondrial dysfunction-related neurodegeneration in vivo, using a mouse model of retinal ganglion cell layer (GCL) degeneration induced by rotenone, a mitochondrial complex I...

متن کامل

Inhibition of mTOR signaling protects photoreceptor cells against serum deprivation by reducing oxidative stress and inducing G2/M cell cycle arrest.

The mammalian target of rapamycin (mTOR) pathway is a crucial cellular signaling hub, which integrates internal and external cues to modulate the cell cycle, protein synthesis and metabolism. The present study hypothesized that inhibiting mTOR signaling may induce cells to enter lower and more stable bioenergetic states, in which neurons have greater resistance to various insults. Neurotrophin ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 18  شماره 

صفحات  -

تاریخ انتشار 2017