Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson–Gilford progeria syndrome

Saxena, Sanjeev; Kumar, Sanjeev

doi:10.1007/s11357-020-00167-3

Cited by 13 publications

(9 citation statements)

References 244 publications

(314 reference statements)

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“…However, quite a few compounds that can prevent their formation have been identified. These compounds (in particular, sulforaphane, metformin, rapamycin) cleave prelamin A and progerin by autophagic degradation [ 924 , 925 ] ( Table 3 ).…”

Section: Pharmacological Interventions Protecting Genomementioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

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Section: Pharmacological Interventions Protecting Genomementioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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“…For protein accumulation diseases such as the laminopathies, HGPS and NDs, removal of the cytotoxic proteins through genetic manipulation would provide cures. The hope for the future is the use of novel technologies, such as CRISPR-Cas9-mediated genome editing [152][153][154], to correct these genetic defects by, for example, silencing the dominant-negative allele of LMNA or upregulating autophagy genes. HGPS mouse models edited by CRISPR-Cas9 have shown the potential of this.…”

Section: Manipulating For Lamina Protein Clearancementioning

confidence: 99%

The Nuclear Lamina: Protein Accumulation and Disease

et al. 2020

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Cellular health is reliant on proteostasis—the maintenance of protein levels regulated through multiple pathways modulating protein synthesis, degradation and clearance. Loss of proteostasis results in serious disease and is associated with aging. One proteinaceous structure underlying the nuclear envelope—the nuclear lamina—coordinates essential processes including DNA repair, genome organization and epigenetic and transcriptional regulation. Loss of proteostasis within the nuclear lamina results in the accumulation of proteins, disrupting these essential functions, either via direct interactions of protein aggregates within the lamina or by altering systems that maintain lamina structure. Here we discuss the links between proteostasis and disease of the nuclear lamina, as well as how manipulating specific proteostatic pathways involved in protein clearance could improve cellular health and prevent/reverse disease.

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“…A previous study reported that the accumulation of progerin in HGPS cells leads to aberrant nuclear morphology, genetic instability, and p53-dependent premature senescence [64] . Progerin and prelamine A inhibition may provide potential therapeutic approaches to the removal of cellular senescence [ 65 , 66 ]. Numerous studies have shown that p53/p21 pathway is involved in regulating cellular senescence 67 , 68 , 69 .…”

Section: Introductionmentioning

confidence: 99%

The emerging role of cellular senescence in complications of COVID-19

Mohiuddin

Kondo

2021

Cancer Treatment and Research Communications

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The coronavirus disease 2019 (COVID-19) pandemic has triggered a sudden global change in healthcare systems. Cancer patients have a higher risk of death from COVID-19 in comparison to patients without cancer. Many studies have stated that various factors, such as older age, frequent exposure to healthcare, and higher smoking rates are responsible for the complications of COVID-19. We hypothesize that side effects of chemotherapy, such as cellular senescence, could worsen COVID-19. Given this situation, in this review, we highlight the updated findings of research investigating the impact of cellular senescence on COVID-19 complications and explored potential therapeutic targets for eliminating senescent cells during the COVID-19 pandemic.

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Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson–Gilford progeria syndrome

Cited by 13 publications

References 244 publications

Genome-Protecting Compounds as Potential Geroprotectors

Genome-Protecting Compounds as Potential Geroprotectors

The Nuclear Lamina: Protein Accumulation and Disease

The emerging role of cellular senescence in complications of COVID-19

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