Apoptosis Signal Regulating Kinase 1 (ASK1):  Potential as a Therapeutic Target for Alzheimer’s Disease

Song, Jeong Sup; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

doi:10.3390/ijms15022119

Cited by 68 publications

(39 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulating evidence suggests that ASK1 may contribute to the pathogenesis of AD and other neurodegenerative disorders by regulating various cellular responses such as apoptosis, cell survival, and differentiation (Song et al ., 2014). …”

Section: Discussionmentioning

confidence: 99%

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Lauretti

Praticò

2015

Aging Cell

View full text Add to dashboard Cite

SummaryAlterations of glucose metabolism have been observed in Alzheimer's disease (AD) brain. Previous studies showed that glucose deprivation increases amyloidogenesis via a BACE‐1‐dependent mechanism. However, no data are available on the effect that this condition may have on tau phosphorylation. In this study, we exposed neuronal cells to a glucose‐free medium and investigated the effect on tau phosphorylation. Compared with controls, cells incubated in the absence of glucose had a significant increase in tau phosphorylation at epitopes Ser202/Thr205 and Ser404, which was associated with a selective activation of the P38 mitogen‐activated protein kinase. Pharmacological inhibition of this kinase prevented the increase in tau phosphorylation, while fluorescence studies revealed its co‐localization with phosphorylated tau. The activation of P38 was secondary to the action of the apoptosis signal‐regulating kinase 1, as its down‐regulation prevented it. Finally, glucose deprivation induced cell apoptosis, which was associated with a significant increase in both caspase 3 and caspase 12 active forms. Taken together, our studies reveal a new mechanism whereby glucose deprivation can modulate AD pathogenesis by influencing tau phosphorylation and suggest that this pathway may be a new therapeutic target for AD.

show abstract

Section: Discussionmentioning

confidence: 99%

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Lauretti

Praticò

2015

Aging Cell

View full text Add to dashboard Cite

show abstract

“…ASK1, a protein kinase of the mitogen-activated protein kinase kinase kinase (MAPKKK) family that initiates the JNK and p38 MAPK signaling cascades is involved in several cellular responses like apoptosis, cell survival, and differentiation. Since it is also activated in response to several stresses including TNF, ER stress, and H 2 O 2 , it is the potential therapeutic target currently [95].…”

Section: Proteins and Peptidesmentioning

confidence: 99%

Apoptosis in Alzheimer’s Disease: An Understanding of the Physiology, Pathology and Therapeutic Avenues

2014

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a devastative neurodegenerative disorder with complex etiology. Apoptosis, a biological process that plays an essential role in normal physiology to oust a few cells and contribute to the normal growth, when impaired or influenced by various factors such as Bcl2, Bax, caspases, amyloid beta, tumor necrosis factor-α, amyloid precursor protein intracellular C-terminal domain, reactive oxygen species, perturbation of enzymes leads to deleterious neurodegenerative disorders like AD. There are diverse pathways that provoke manifold events in mitochondria and endoplasmic reticulum (ER) to execute the process of cell death. This review summarizes the crucial apoptotic mechanisms occurring in both mitochondria and ER. It gives substantial summary of the diverse mechanisms studied in vivo and in vitro. A brief account on neuroprotection of several bioactive components, flavonoids and antioxidants of plants against apoptotic events of both mitochondria and ER in both in vitro and in vivo has been discussed. In light of this, the burgeoning need to develop animal models to study the efficacy of various therapeutic effects has been accentuated.

show abstract

“…1 Conversely the ER stress pathway can activate tau kinases such as apoptosis signal-regulating kinase 1, JNK, and glycogen synthase kinase-3b (GSK3b). 8,38,48 These important costimulatory interactions connect ER stress in interplay with chronic neurodegenerative diseases. In addition, phosphorylated PERK has been colocalized with tau in diseases such as Alzheimer's disease and supranuclear palsy.…”

mentioning

confidence: 99%

Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy

Lucke‐Wold

Turner

Logsdon

et al. 2016

JNS

View full text Add to dashboard Cite

abbreviatioNs ATF6 = activating transcription factor 6; BiP = binding immunoglobulin protein; CHOP = C/EBP homology protein; CTE = chronic traumatic encephalopathy; DAB = diaminobenzidine; DHA = docosahexaenoic acid; ER = endoplasmic reticulum; GADD34 = growth arrest and DNA damage-inducible protein 34; GSK3b = glycogen synthase kinase-3b; IHC = immunohistochemistry; IRE1a = inositol requiring enzyme 1a; JNK = c-Jun N-terminal kinase; NFL = National Football League; PBS = phosphate-buffered saline; PERK = protein kinase RNA-like ER kinase; PHF = paired helical filament; p-eIF2a = phosphorylated eukaryotic initiation factor 2a; TBI = traumatic brain injury; WWE = World Wrestling Entertainment; XBP1 = X-box binding protein 1. obJective Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. methods The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. results The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3b. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p < 0.05), improved cognition (t = 6.532, p < 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p < 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. coNclusioNs Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.

show abstract

Apoptosis Signal Regulating Kinase 1 (ASK1): Potential as a Therapeutic Target for Alzheimer’s Disease

Cited by 68 publications

References 84 publications

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Apoptosis in Alzheimer’s Disease: An Understanding of the Physiology, Pathology and Therapeutic Avenues

Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy

Contact Info

Product

Resources

About