Movement of the endoplasmic reticulum is driven by multiple classes of vesicles marked by Rab-GTPases DOI Creative Commons

Allison Langley,

Sarah Abeling-Wang,

Erinn Wagner

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 15, 2024

Peripheral endoplasmic reticulum (ER) tubules move along microtubules to interact with various organelles through membrane contact sites (MCS). Traditionally, ER moves by either sliding stable via molecular motors or attaching the plus ends of dynamic tip attachment complexes (TAC). A recently discovered third process, hitchhiking, involves motile vesicles pulling microtubules. Previous research showed that hitchhikes on Rab5- and Rab7-marked endosomes, but it is uncertain if other Rab-vesicles can do same. In U2OS cells, we screened Rabs for their ability cotransport found post-Golgi marked Rab6 (isoforms a b). Rab6-ER hitchhiking occurs independently ER-endolysosome contacts TAC-mediated movement. Disrupting motility Rab6-vesicles reduces overall Conversely, relocating these cell periphery causes peripheral accumulation, indicating Rab6-vesicle crucial subset movements. Proximal TGN46 are involved in while (Rabs 8/10/11/13/14) not essential Our further analysis finds Golgi Rab1 also capable driving Taken together, our findings suggest significant mode

Язык: Английский

The Interplay Between Endoplasmic Reticulum Stress and Ferroptosis in Neurological Diseases DOI

Tianyu Zhai,

Bingbing Wang,

Caizhen Shi

и другие.

Neurochemical Research, Год журнала: 2025, Номер 50(2)

Опубликована: Фев. 10, 2025

Язык: Английский

Процитировано

1

Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson’s Disease According to the Single-Neuron Degeneration Model DOI Creative Commons
Sandro Huenchuguala, Juan Segura‐Aguilar

Biomolecules, Год журнала: 2024, Номер 14(6), С. 673 - 673

Опубликована: Июнь 8, 2024

One of the biggest problems in treatment idiopathic Parkinson’s disease is lack new drugs that slow its progression. L-Dopa remains star drug this disease, although it induces severe side effects. The failure clinical studies with depends on use preclinical models based neurotoxins do not represent what happens since they induce rapid and expansive neurodegeneration. We have recently proposed a single-neuron degeneration model for requires years to accumulate enough lost neurons onset motor symptoms. This excessive formation aminochrome during neuromelanin synthesis surpass neuroprotective action enzymes DT-diaphorase glutathione transferase M2-2, which prevent neurotoxic effects aminochrome. Although an effect, stereotaxic injection endogenous neurotoxin cannot be used generate animal. Therefore, aim review evaluate strategies pharmacologically increasing expression DT diaphorase GSTM2-2 molecules vesicular monoamine transporter 2, such as pramipexole.

Язык: Английский

Процитировано

6

Endoplasmic Reticulum Proteins Impact Penetrance in a Pink1-Mutant Drosophila Model DOI Open Access
Melissa Vos, Fabian Ott,

Hawwi Gillo

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 979 - 979

Опубликована: Янв. 24, 2025

Parkinson’s disease (PD) is a neurodegenerative disorder with high variability of age at onset, severity, and progression. This suggests that other factors, including genetic, environmental, or biological are play in PD. The loss PINK1 causes recessive form PD typically fully penetrant; however, it features wide range further supporting the existence protective endogenous exogenous, to role. Pink1 Drosophila melanogaster results locomotion deficits, also observed PINK1-related humans. In flies, deficiency induces defects ability fly; nonetheless, around ten percent mutant flies still capable flying, indicating advantageous factors affecting penetrance exist flies. Here, we aimed identify mechanisms underlying this reduced Pink1-deficient We performed genetic screening pink1-mutant RNA expression alterations flying ability. most important processes involved were transcriptional translational activities, endoplasmic reticulum (ER) regulation, flagellated movement microtubule organization. validated two ER-related proteins, zonda windbeutel, positively affect Thus, our data suggest these influencing them may be beneficial for deficiency.

Язык: Английский

Процитировано

0

Critical role of microRNAs in cellular quality control during brain aging and neurological disorders: Interplay between autophagy and proteostasis DOI Creative Commons

Rajesh Tamatta,

Abhishek Kumar Singh

Life Sciences, Год журнала: 2025, Номер 369, С. 123563 - 123563

Опубликована: Март 13, 2025

A decline in cellular quality control mechanisms is one of the processes brain aging. Autophagy and proteostasis are two regulatory that maintain component turnover to preserve homeostasis, optimal function, neuronal health by eliminating damaged aggregated proteins preventing neurodegenerative disorders (NDDs). Impaired autophagy significant hallmarks aging many age-related NDDs. MicroRNAs noncoding RNA molecules have recently been shown be essential for regulating several biological processes, such as autophagy, proteostasis, differentiation, development targeting mRNA's 3'untranslated region (3'UTR). During aging, miRNAs dysregulate resulting abnormal activity protein aggregation, a characteristic This review highlights complex interactions orchestration autophagy. dysregulation impairs autophagic flux accelerates disorders, neuroinflammation, neurodegeneration. Understanding among miRNAs, novel therapeutics

Язык: Английский

Процитировано

0

Endoplasmic Reticulum Stress: Implications in Diseases DOI
Neha Sylvia Walter, Varun Gorki, Rishi Bhardwaj

и другие.

The Protein Journal, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Язык: Английский

Процитировано

0

Parkinson’s Disease: The Neurodegenerative Enigma Under the “Undercurrent” of Endoplasmic Reticulum Stress DOI Open Access
Xiangrui Kong, Tingting Liu, Jianshe Wei

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3367 - 3367

Опубликована: Апрель 3, 2025

Parkinson's disease (PD), a prevalent neurodegenerative disorder, demonstrates the critical involvement of endoplasmic reticulum stress (ERS) in its pathogenesis. This review comprehensively examines role and molecular mechanisms ERS PD. represents cellular response triggered by imbalances (ER) homeostasis, induced factors such as hypoxia misfolded protein aggregation, which activate unfolded (UPR) through inositol-requiring enzyme 1 (IRE1), kinase R-like (PERK), activating transcription factor 6 (ATF6) pathways. Clinical, animal model, studies have consistently demonstrated strong association between PD ERS. Abnormal expression ERS-related molecules patients' brains cerebrospinal fluid (CSF) correlates with progression. In models (e.g., Drosophila mice), inhibition alleviates dopaminergic neuronal damage. Cellular experiments reveal that PD-mimicking pathological conditions induce ERS, while interactions mitochondrial dysfunction promote apoptosis. Mechanistically, (1) aggregation α-synuclein (α-syn) mutually reinforce neuron damage; (2) leucine-rich repeat 2 (LRRK2) gene mutations thrombospondin-1 (THBS1)/transforming growth beta (TGF-β1) interactions; (3) Parkin PTEN-induced (PINK1) regulate Furthermore, interacts dysfunction, oxidative stress, neuroinflammation to exacerbate injury. Emerging therapeutic strategies show significant potential, including artificial intelligence (AI)-assisted drug design targeting pathways precision medicine approaches exploring non-pharmacological interventions personalized electroacupuncture. Future research should focus on elucidating identifying novel targets develop more effective treatments for patients, ultimately improving their quality life.

Язык: Английский

Процитировано

0

Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review DOI
Maneesh Mohan, Ashi Mannan, Thakur Gurjeet Singh

и другие.

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Апрель 9, 2025

Язык: Английский

Процитировано

0

Endurance Training Alleviates Metabolic-associated Fatty-liver Disease (MAFLD)-related Testicular Impairments via ER Stress Regulation DOI

Vahid Kazemizadeh,

Nastaran Teimouri,

Azita Faramarzi

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 18, 2025

Abstract Metabolic-associated fatty liver disease (MAFLD), the most prevalent disorder globally, affects 20–40% of population and presents significant health challenges. Studies link MAFLD to male reproductive dysfunction, highlighting need for effective interventions. This study investigates impact on testicular function evaluates protective role endurance training, with a focus PERK-EIF2α-ATF4 signaling pathway. Forty-four rats were allocated into two dietary groups (n = 22 each): standard diet control group (C) high-fat supplemented fructose water (FL). After 17 weeks, histological analysis confirmed development in FL group, while showed no pathological changes. Each was further subdivided sedentary endurance-trained (T) subgroups 10 per subgroup), resulting four experimental groups: C, C + T, FL. At end research, thyroid hormones (T3, T4, TSH), sex (testosterone, LH, FSH) as well PERK, EIF2α AFT4 expression assessed. Our result indicated that led weight gain, disrupted serum levels hormones, impaired hormone profiles. Additionally, triggered ER stress, evidenced by dysregulated genes Remarkably, training mitigated these adverse effects normalizing hormonal profiles restoring stress-related genes. These findings highlight critical stress MAFLD-induced dysfunction.

Язык: Английский

Процитировано

0

Neuroprotective effects of punicalagin and/or micronized zeolite clinoptilolite on manganese‐induced Parkinson's disease in a rat model: Involvement of multiple pathways DOI Creative Commons
Karema Abu‐Elfotuh,

Ashwaq N. Abbas,

Mazin A. A. Najm

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(10)

Опубликована: Окт. 1, 2024

Manganism, a central nervous system dysfunction correlated with neurological deficits such as Parkinsonism, is caused by the substantial collection of manganese chloride (MnCl

Язык: Английский

Процитировано

3

Movement of the endoplasmic reticulum is driven by multiple classes of vesicles marked by Rab-GTPases DOI Creative Commons

Allison Langley,

Sarah Abeling-Wang,

Erinn Wagner

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 15, 2024

Peripheral endoplasmic reticulum (ER) tubules move along microtubules to interact with various organelles through membrane contact sites (MCS). Traditionally, ER moves by either sliding stable via molecular motors or attaching the plus ends of dynamic tip attachment complexes (TAC). A recently discovered third process, hitchhiking, involves motile vesicles pulling microtubules. Previous research showed that hitchhikes on Rab5- and Rab7-marked endosomes, but it is uncertain if other Rab-vesicles can do same. In U2OS cells, we screened Rabs for their ability cotransport found post-Golgi marked Rab6 (isoforms a b). Rab6-ER hitchhiking occurs independently ER-endolysosome contacts TAC-mediated movement. Disrupting motility Rab6-vesicles reduces overall Conversely, relocating these cell periphery causes peripheral accumulation, indicating Rab6-vesicle crucial subset movements. Proximal TGN46 are involved in while (Rabs 8/10/11/13/14) not essential Our further analysis finds Golgi Rab1 also capable driving Taken together, our findings suggest significant mode

Язык: Английский

Процитировано

0