The roles of the proteasome pathway in signal transduction and neurodegenerative diseases

Chen, Jiaojiao; Lin, Fang; Qin, Zheng‐Hong

doi:10.1007/s12264-008-0183-6

Cited by 30 publications

(17 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Amyloid peptide can impair the proteasome, whose activity was found to be lower in AD brains than in age-matched controls [59], hence the altered levels of p53 in our experimental model could be also due to proteasomal impairment.…”

Section: Discussionmentioning

confidence: 73%

PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage

et al. 2013

View full text Add to dashboard Cite

Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ25–35 fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ25–35 induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ25–35 exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ25–35 induces DNA damage which in turn activates PARP-1. Challenge with Aβ25–35 is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ25–35 via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed.

show abstract

Section: Discussionmentioning

confidence: 73%

PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage

et al. 2013

View full text Add to dashboard Cite

show abstract

“…These proteins are identified by ER-specific E3 ligases that mediate polyubiquitination of the misfolded proteins on the cytosolic side of ER and are lastly degraded by proteasomes (Chen et al, 2008). Degradation of Ubi-proteins is ATP-dependent and these proteins act as signals to induce heat shock transcription factors to stimulate expression of molecular chaperones (Voellmy, 2004) that will inhibit protein accumulation.…”

Section: Mechanisms Concerning Ischemic Conditioningmentioning

confidence: 99%

Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke

Wang

Reis

Applegate

et al. 2015

Experimental Neurology

View full text Add to dashboard Cite

In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre- or post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stoke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post- ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on those recently reported methodological and mechanistic discoveries in the realm of ischemic conditioning. Due to the varied time differences of ischemic conditioning in different animal models and clinical trials, it is important to define optimal timing to achieve the best conditioning induced neuroprotection. This brings not only an opportunity in treatment of stroke, but challenges as well, as data is just becoming available and the procedures are not yet optimized. The purpose of this review is to shed light on exploiting these ischemic conditioning modalities to protect the cerebrovascular system against diverse injuries and neurodegenerative disorders.

show abstract

“…These evidence provides strong evidence that there is a linkage between the age-dependent accumulation of oxidized proteins and the loss in brain physiological functions. It has recently been proposed that a primary mechanism leading to neuronal cell death in ageing and common neurodegenerative disorders is interference with proteasome function [28]. The major neurodegenerative diseases, Alzheimer disease (AD), Parkinson's Disease (PD), amytrophic lateral sclerosis (ALS), Huntington's disease (HD) and Freidreich's ataxia (FA) are all associated with the presence of abnormal proteins [16,29].…”

Section: The ''Free Radical Hypothesis'' Of Agingmentioning

confidence: 99%

Cellular Stress Responses, Mitostress and Carnitine Insufficiencies as Critical Determinants in Aging and Neurodegenerative Disorders: Role of Hormesis and Vitagenes

et al. 2010

View full text Add to dashboard Cite

The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. A prediction of this theory is that, among species, differential rates of aging may be apparent on the basis of intrinsic differences in oxidative damage accrual. Although widely accepted, there is a growing number of exceptions to this theory, most contingently related to genetic model organism investigations. Proteins are one of the prime targets for oxidative damage and cysteine residues are particularly sensitive to reversible and irreversible oxidation. The adaptation and survival of cells and organisms requires the ability to sense proteotoxic insults and to coordinate protective cellular stress response pathways and chaperone networks related to protein quality control and stability. The toxic effects that stem from the misassembly or aggregation of proteins or peptides, in any cell type, are collectively termed proteotoxicity. Despite the abundance and apparent capacity of chaperones and other components of homeostasis to restore folding equilibrium, the cell appears poorly adapted for chronic proteotoxic stress which increases in cancer, metabolic and neurodegenerative diseases. Pharmacological modulation of cellular stress response pathways has emerging implications for the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. A critical key to successful medical intervention is getting the dose right. Achieving this goal can be extremely challenging due to human inter-individual variation as affected by age, gender, diet, exercise, genetic factors and health status. The nature of the dose response in and adjacent to the therapeutic zones, over the past decade has received considerable advances. The hormetic dose-response, challenging long-standing beliefs about the nature of the dose-response in a lowdose zone, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses, including carnitines. This paper describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways, including the possible signaling mechanisms by which the carnitine system, by interplaying metabolism, mitochondrial energetics and activation of critical vitagenes, modulates signal transduction cascades that confer cytoprotection against chronic degenerative damage associated to aging and neurodegenerative disorders.

show abstract

The roles of the proteasome pathway in signal transduction and neurodegenerative diseases

Cited by 30 publications

References 94 publications

PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage

PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage

Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke

Cellular Stress Responses, Mitostress and Carnitine Insufficiencies as Critical Determinants in Aging and Neurodegenerative Disorders: Role of Hormesis and Vitagenes

Contact Info

Product

Resources

About