The role of lysophosphatidic acid and its receptors in corneal nerve regeneration DOI Creative Commons
Maryam Kheyrollah, Nicola Brandt, Anja U. Bräuer

et al.

The Ocular Surface, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

The integrity of corneal nerves is critical for ocular surface health, and damages can lead to Neurotrophic Keratopathy (NK). Despite the regenerative abilities peripheral nerve system (PNS), regeneration often incomplete, underlying mechanisms are poorly understood. This study aims identify potential factors that enhance NK treatment, with a focus on Lysophosphatidic acid (LPA). Thus, effect LPA its pathways in investigated detail using vitro mouse sensory neurons. To elucidate impact as well reveal responsible receptor, several functional assays siRNA-based knock-down experiments were conducted. Additionally, possible changes mRNA levels. LPA-treated neurons significantly reduced fiber growth. However, LPAR2 knockdown (Lpar2-KD) following treatment showed significant increase length. demonstrated enhanced levels Lpar2 mRNA. On other hand, indicators such Ngf, Gap-43, Cdc42, along downstream signaling components like Pi3k Ras, elevated Lpar2-KD In conclusion, this elucidates inhibitory effects outgrowth Furthermore, was identified receptor effect. might be promising therapeutic approach neuronal patients NK.

Language: Английский

Novel frontiers in neuroprotective therapies in glaucoma: Molecular and clinical aspects DOI
Alessandra Boccaccini,

Dario Cavaterra,

Carmela Carnevale

et al.

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 94, P. 101225 - 101225

Published: Nov. 24, 2023

Language: Английский

Citations

9
Aging-Related Protein Alterations in the Brain DOI
Rafay Ali Syed,

Mahnoor Hayat,

Hammad Qaiser

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 99(s1), P. S5 - S22

Published: Feb. 6, 2024

Aging is an intrinsic aspect of organism's life cycle and characterized by progressive physiological decline increased susceptibility to mortality. Many age-associated disorders, including neurological are most commonly linked with the aging process, such as Alzheimer's disease (AD). This review aims provide a comprehensive overview effects AD on molecular pathways levels different proteins in brain, metalloproteins, neurotrophic factors, amyloid proteins, tau proteins. caused aggregation brain. Factors metal ions, protein ligands, oligomerization state precursor significantly influence proteolytic processing amyloid-β (AβPP). Tau, disordered cytosolic protein, serves principal microtubule-associated mature neurons. patients exhibit decreased nerve growth factor within their nervous systems cerebrospinal fluid. Furthermore, significant increase brain-derived resulting from neuroprotective effect glial cell line-derived suggests that synergistic action these plays role inhibiting neuronal degeneration atrophy. The mechanism through which Aβ AβPP govern Cu2+ transport other ion pools requires elucidation future studies. A understanding varying may hold potential for development novel diagnostic therapeutic methods treatment AD.

Language: Английский

Citations

3
Suppression of autophagy induces senescence in the heart DOI Creative Commons
Peiyong Zhai, Eun‐Ah Sung,

Yuka Shiheido‐Watanabe

et al.

Journal of Molecular and Cellular Cardiology, Journal Year: 2024, Volume and Issue: 195, P. 83 - 96

Published: Aug. 6, 2024

Aging is a critical risk factor for heart disease, including ischemic disease and failure. Cellular senescence, characterized by DNA damage, resistance to apoptosis the senescence-associated secretory phenotype (SASP), occurs in many cell types, cardiomyocytes. Senescence precipitates aging process surrounding cells organ through paracrine mechanisms. Generalized autophagy, which degrades cytosolic materials non-selective manner, decreased during heart. This decrease causes deterioration of cellular quality control mechanisms, facilitates negatively affects lifespan animals, mice. Although suppression generalized autophagy could promote it remains unclear whether directly stimulates senescence cardiomyocytes, which, turn, promotes myocardial dysfunction We addressed this question using mouse models with loss function. Suppression general cardiac-specific Atg7 knockout (Atg7cKO) mice caused accumulation senescent Induction via downregulation was also observed chimeric KO cultured cardiomyocytes vitro, suggesting that effect upon induction autonomous. ABT-263, senolytic agent, reduced number myocytes improved cardiac function Atg7cKO were doxorubicin-treated hearts, where reactivation alleviated dysfunction. These results suggest induces turn

Language: Английский

Citations

3
Combination of blockade of endothelin signalling and compensation of IGF1 expression protects the retina from degeneration DOI Creative Commons

Naoya Shigesada,

Naoya Shikada,

Manabu Shirai

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 22, 2024

Abstract Retinitis pigmentosa (RP) and macular dystrophy (MD) cause severe retinal dysfunction, affecting 1 in 4000 people worldwide. This disease is currently assumed to be intractable, because effective therapeutic methods have not been established, regardless of genetic or sporadic traits. Here, we examined a RP mouse model which the Prominin-1 ( Prom1 ) gene was deficient investigated molecular events occurring at outset dysfunction. We extracted Prom1-deficient retina subjected light exposure for short time, conducted single-cell expression profiling, compared with without stimuli. identified cells genes whose levels change directly response Among altered by stimulation, Igf1 decreased rod photoreceptor astrocytes under light-stimulated condition. Consistently, insulin-like growth factor (IGF) signal weakened cells. The recovery adeno-associated virus (AAV) prevented cell death, its treatment combination endothelin receptor antagonist led blockade abnormal glial activation promotion glycolysis, thereby resulting improvement functions, as assayed electroretinography. additionally demonstrated that attenuation mammalian/mechanistic target rapamycin (mTOR), mediates IGF signalling, leads complications maintaining homeostasis. Together, propose combinatorial manipulation distinct mechanisms useful maintenance

Language: Английский

Citations

2
Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice DOI Creative Commons
Lue Xiang,

Qiaoli Yang,

Bintao Xie

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2023, Volume and Issue: 64(12), P. 2 - 2

Published: Sept. 1, 2023

Degeneration of retinal photoreceptors is frequently observed in diverse ciliopathy disorders, and photoreceptor cilium gates the molecular trafficking between inner outer segment (OS). This study aims to generate a homozygous global Cep250 knockout (KO) mouse resulting phenotype.We used KO mice untargeted metabolomics uncover potential mechanisms underlying degeneration. Long-term follow-up studies using optical coherence tomography (OCT) electroretinography (ERG) were performed.OCT ERG results demonstrated gradual thinning nuclear layer (ONL) progressive attenuation scotopic responses Cep250-/- mice. More TUNEL signal was ONL these Immunostaining selected OS proteins revealed mislocalization Interestingly, analysis arginine-related metabolic pathways altered enriched Mis-localization key protein arginine metabolism pathway, arginase 1 (ARG1), further supports this model. Moreover, adeno-associated virus (AAV)-based knockdown Arg1 led similar architectural functional alterations wild-type retinas.Altogether, suggest that dysregulated contributes degeneration Our findings provide novel insights increase understanding disorders.

Language: Английский

Citations

6
Unlocking the role of lactate: metabolic pathways, signaling, and gene regulation in postmitotic retinal cells DOI Creative Commons
Raju V. S. Rajala, Ammaji Rajala

Frontiers in Ophthalmology, Journal Year: 2023, Volume and Issue: 3

Published: Nov. 8, 2023

The Warburg effect, which was first described a century ago, asserts that mitotic tumor cells generate higher quantities of lactate. Intriguingly, even in typical physiological circumstances, postmitotic retinal photoreceptor also produce elevated levels Initially classified as metabolic waste, lactate has since gained recognition significant intracellular signaling mediator and extracellular ligand. This current review endeavors to provide concise overview discourse on the following topics: localization lactate-producing enzymes, functional significance these functions lactate, its impact gene expression photoreceptors cells.

Language: Английский

Citations

6
Therapeutic strategies for glaucoma and optic neuropathies DOI Creative Commons
Jung Lo,

Kamakshi Mehta,

Armaan Dhillon

et al.

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 94, P. 101219 - 101219

Published: Oct. 13, 2023

Language: Английский

Citations

5
Transgenic silkworm expressing bioactive human ciliary neurotrophic factor for biomedical application DOI

Weiqun Lan,

Wenjing Geng,

Xuechun Jiang

et al.

Insect Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Abstract Ciliary neurotrophic factor (CNTF) acts as a potent neuroprotective agent in neuronal survival and regeneration, can also induce the differentiation of several stem cells into neurons, which highlights broad application CNTF biomedicine. However, large‐scale production bioactive recombinant human protein remains to be explored. Herein, this study aims express on large scale by genetically engineering silk gland bioreactor silkworm. Our results showed that was successfully expressed middle (MSG) silkworm, secreted silks with amount 3.2 mg/g cocoons. The fabrication CNTF‐functionalized material able promote proliferation migration neural when compared natural protein. Importantly, functional could facilitate neurite outgrowth mouse retinal ganglion cell (RGC‐5) cells. All these data demonstrated high bioactivity MSG further different materials will give biomedical applications tissue neuroregeneration.

Language: Английский

Citations

1
The dichotomic role of cytokines in aging DOI
Rafael Cardoso Maciel Costa Silva

Biogerontology, Journal Year: 2024, Volume and Issue: 26(1)

Published: Dec. 2, 2024

Language: Английский

Citations

1
Bidirectional causality of physical exercise in retinal neuroprotection DOI Creative Commons
Stephen Kugbere Agadagba, Suk-Yu Yau, Ying Liang

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(12), P. 3400 - 3415

Published: Dec. 16, 2024

Physical exercise is recognized as an effective intervention to improve mood, physical performance, and general well-being. It achieves these benefits through cellular molecular mechanisms that promote the release of neuroprotective factors. Interestingly, reduced levels have been implicated in several central nervous system diseases, including ocular disorders. Emerging evidence has suggested are significantly lower individuals with diseases such glaucoma, age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy. may a effect on retina. Therefore, association between involve bidirectional causal relationship whereby visual impairment leads decreased exacerbates development disease. In this review, we summarize linking eye disease identify potential mediators exercise-induced retinal neuroprotection. Finally, discuss future directions for preclinical clinical research health.

Language: Английский

Citations

1