Neuroprotective Effects of GV1001 in Animal Stroke Model and Neural Cells Subject to Oxygen-Glucose Deprivation/Reperfusion Injury

Kwon, Hyuk Sung; Kim, Ye Eun; Park, Hyun‐Hee; Son, Jeong-Woo; Choi, Hojin; Lee, Young Joo; Kim, Ho; Lee, Kyu-Yong; Koh, Seong‐Ho

doi:10.5853/jos.2021.00626

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…It was suggested that TERT protects neurons from apoptosis induced by various stresses including cerebral hypoxia-ischemia by increasing the expression rate of Bcl-2/Bax and decreasing ROS production [123] . Zhang et al verified that rapid nuclear stimulation of the cerebellum could achieve neuroprotection by upregulating the expression of TERT, and then increasing telomerase activity, in adult male SD rats [126] . Kwon et al demonstrated the neuroprotective effect of GV1001 against focal cerebral ischemia-reperfusion injury and OGD/reoxygenation-induced injury in NSCs and cortical neurons in rats [127] .…”

Section: Telomeres and Telomerase And Hypoxic-ischemic Encephalopathymentioning

confidence: 99%

Potential roles of telomeres and telomerase in neurodegenerative diseases

Shao,

Wang,

et al. 2024

Ageing Neur Dis

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Telomeres, essential DNA-protein complexes located at chromosome ends, play a critical role in preventing chromosome fusion, recombination, and degradation, thus ensuring genomic stability. When telomeres reach a limiting shortened length, they will activate DNA damage checkpoints, stop cell division and trigger replicative senescence. Telomerase is composed of RNA and protein, which can synthesize telomeres repeat sequences, and elongate telomeres. Studies have shown that telomere length (TL) and telomerase activity are closely involved in aging, aging-related degenerative diseases, and tumors. Neurodegenerative diseases (NDDs) are one of the major aging-related diseases caused by both genetic and environmental factors, characterized by insidious onset, difficult diagnosis, irreversible disease progression, and lack of effective treatments, which brings a heavy burden to society and families. Currently, many studies have noted variations in leukocyte telomere length (LTL) and telomerase activity in NDDs, suggesting a vital role for telomeres and telomerase in NDD pathogenesis. This review explores the relationship between TL and NDDs, examines telomerase as a potential therapeutic target, and discusses emerging biomarkers and intervention strategies for NDD diagnosis and treatment.

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Section: Telomeres and Telomerase And Hypoxic-ischemic Encephalopathymentioning

confidence: 99%

Potential roles of telomeres and telomerase in neurodegenerative diseases

Shao,

Wang,

et al. 2024

Ageing Neur Dis

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“…For example, GV1001, a peptide vaccine derived from the active site sequence of hTERT, initially developed as an anti-cancer agent, was later found to also have anti-aging effects. In particular, it was able to relieve the effects of Aβ and oxygen–glucose deprivation/reoxygenation-mediated oxidative stress by inhibiting the production of ROS [ 119 , 120 ]. GV1001 also promoted neuronal regeneration by restoring the PI3k-mTOR pathway, which is involved in cell survival and proliferation [ 121 ].…”

Section: Therapeutic Opportunitiesmentioning

confidence: 99%

Exploring the Causal Relationship Between Telomere Biology and Alzheimer’s Disease

Kuan

Fauzi

et al. 2023

Mol Neurobiol

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Telomeres, also known as the “protective caps” of our chromosomes, shorten with each cell cycle due to the end replication problem. This process, termed telomere attrition, is associated with many age-related disorders, such as Alzheimer’s disease (AD). Despite the numerous studies conducted in this field, the role of telomere attrition in the onset of the disease remains unclear. To investigate the causal relationship between short telomeres and AD, this review aims to highlight the primary factors that regulate telomere length and maintain its integrity, with an additional outlook on the role of oxidative stress, which is commonly associated with aging and molecular damage. Although some findings thus far might be contradictory, telomere attrition likely plays a crucial role in the progression of AD due to its close association with oxidative stress. The currently available treatments for AD are only symptomatic without affecting the progression of the disease. The components of telomere biology discussed in this paper have previously been studied as an alternative treatment option for several diseases and have exhibited promising in vitro and in vivo results. Hence, this should provide a basis for future research to develop a potential therapeutic strategy for AD. Graphical Abstract (Created with BioRender.com)

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“…GV1001 is a small peptide containing 16 amino acids that mimics a fragment of the active catalytic site of human telomerase reverse transcriptase (hTERT). GV1001 has been previously reported to have various biological functions, including antioxidant, antiinflammatory, anti-aging, anti-apoptotic, and mitochondrial stabilisation effects, mimicking the extratelomeric function of hTERT [14][15][16]. Based on these beneficial effects, GV1001 was applied in a phase II clinical trial for the treatment of moderate to severe AD, and the results showed that a significant improvement in cognitive function was observed in patients with moderate to severe AD treated with GV1001, at weeks 12 and 24 [17].…”

Section: Introductionmentioning

confidence: 99%

GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects

Park,

Kwon,

Lee

et al. 2024

Aging

Self Cite

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GV1001, which mimics the activity of human telomerase reverse transcriptase, protects neural cells from amyloid beta (Aβ) toxicity and other stressors through extra-telomeric function, as noted in our prior in vitro studies. As per a recent phase II clinical trial, it improves cognitive function in patients with moderate to severe dementia. However, the underlying protective mechanisms remain unclear. This study aimed to investigate the effects of GV1001 on neurodegeneration, senescence, and survival in triple transgenic Alzheimer’s disease (3xTg-AD) mice. GV1001 (1 mg/kg) was subcutaneously injected into old 3xTg-AD mice thrice a week until the endpoint for sacrifice, and survival was analysed. Magnetic resonance imaging (MRI) and Prussian blue staining (PBS) were performed to evaluate entry of GV1001 entrance into the brain. Diverse molecular studies were performed to investigate the effect of GV1001 on neurodegeneration and cellular senescence in AD model mice, with a particular focus on BACE, amyloid beta 1-42 (Aβ 1-42 ), phosphorylated tau, volume of dentate gyrus, β-galactosidase positive cells, telomere length, telomerase activity, and ageing-associated proteins. GV1001 crossed the blood-brain barrier, as confirmed by assessing the status of ferrocenecarboxylic acid-conjugated GV1001 using magnetic resonance imaging and PBS. GV1001 increased the survival of 3xTg-AD mice. It decreased BACE and Aβ 1-42 levels, neurodegeneration (i.e., reduced CA1, CA3 and dentate gyrus volume, decreased levels of senescence-associated β-galactosidase positive cells, and increased telomere length and telomerase activity), and levels of ageing-associated proteins. We suggest that GV1001 exerts anti-ageing effects in 3xTg-AD mice by reducing neurodegeneration and senescence, which contributes to improved survival.

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Neuroprotective Effects of GV1001 in Animal Stroke Model and Neural Cells Subject to Oxygen-Glucose Deprivation/Reperfusion Injury

Cited by 5 publications

References 32 publications

Potential roles of telomeres and telomerase in neurodegenerative diseases

Potential roles of telomeres and telomerase in neurodegenerative diseases

Exploring the Causal Relationship Between Telomere Biology and Alzheimer’s Disease

GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects

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