Effect of Porcine Oviductal Fluid-Derived Extracellular Vesicle Supplementation on in Vitro Embryonic Developmental Competence and the Production Efficiency of Cloned Pigs DOI
Jun-Hyeong Kim, Joohyun Shim, Nayoung Ko

et al.

Published: Jan. 1, 2024

Language: Английский

N-acetyl-l-leucine lowers pS129-synuclein and improves synaptic function in models of Parkinson’s disease DOI
Pingping Song, Rossella Franchini, Chuyu Chen

et al.

Published: April 9, 2025

Abstract N-acetyl-L-leucine (NALL), a derivative of the branched-chain amino acid leucine, has shown therapeutic potential in neurodegenerative diseases, including prodromal stages Parkinson’s disease (PD). However, mechanism its protective effects been largely unknown. Using discovery-based proteomics, we found that treatment with NALL led to upregulation lysosomal, mitochondrial, and synaptic proteins PD patient-derived dopaminergic neurons. reduced levels pathological pS129-alpha-synuclein neurons from patients harboring GBA1 or LRRK2 mutations. This decrease pS129-syn was dependent on serine protease HTRA1 induced by also upregulated expression wild-type parkin both mutant neurons, leading an increase functional dopamine transporter membrane-associated synaptojanin-1, suggesting improved function. Furthermore, LRRK2R1441C knock-in mice decreased pS129-alpha-synuclein, increased dopamine-dependent motor learning deficits. These findings highlight α-synuclein pathology function vulnerable

Language: Английский

Citations

0
Effect of porcine oviductal fluid-derived extracellular vesicle supplementation on in vitro embryonic developmental competence and the production efficiency of cloned pigs DOI
Jun-Hyeong Kim, Joohyun Shim, Nayoung Ko

et al.

Theriogenology, Journal Year: 2025, Volume and Issue: 242, P. 117442 - 117442

Published: April 11, 2025

Language: Английский

Citations

0
Keratinocyte-derived exosomes in painful diabetic neuropathy DOI Creative Commons
James S. Coy-Dibley,

Nirupa D. Jayaraj,

Dongjun Ren

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

ABSTRACT Painful diabetic neuropathy (PDN) is a challenging complication of diabetes with patients experiencing painful and burning sensation in their extremities. Existing treatments provide limited relief without addressing the underlying mechanisms disease. PDN involves gradual degeneration nerve fibers skin. Keratinocytes, most abundant epidermal cell type, are closely positioned to cutaneous terminals, suggesting possibility bi-directional communication. Exosomes small extracellular vesicles released from many types that mediate The role keratinocyte-derived exosomes (KDEs) influencing signaling between skin terminals contribution genesis has not been explored. In this study, we characterized KDEs well-established high-fat diet (HFD) mouse model using primary adult keratinocyte cultures. We obtained highly enriched through size exclusion chromatography then analyzed molecular cargo proteomic analysis RNA sequencing. found significant differences protein microRNA content HFD compared control mice on regular (RD), including pathways involved axon guidance synaptic transmission. Additionally, an vivo conditional vesicle (EV) reporter model, demonstrated epidermal-originating GFP-tagged retrogradely trafficked into DRG neuron body. Overall, our study presents potential novel mode communication keratinocytes neurons skin, revealing possible for contributing axonal underlies neuropathic pain PDN. Moreover, therapeutic targets developing more effective, disease-modifying, better-tolerated topical interventions suffering PDN, one common untreatable peripheral neuropathies.

Language: Английский

Citations

3
The molecular diversity of hippocampal regions and strata at synaptic resolution revealed by integrated transcriptomic and proteomic profiling DOI Creative Commons
Eva Kaulich,

Quinn Waselenchuk,

N Furst

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

ABSTRACT The molecular diversity of neurons and their synapses underlies the different responses plasticity profiles that drive all neural circuits behavior. While extent this has been partially revealed by transcriptomic proteomic profiling, combined studies neuronal transcripts proteins are limited. Here, we used microdissection mouse hippocampal subregions CA1 strata fluorescence-activated synaptosome sorting (FASS) to characterize from compartments with synaptic resolution. Parallel RNA-seq LC-MS/MS microdissections identified over 15,000 mRNA 10,000 proteins, revealing thousands local enrichment such as classes glutamate receptors voltage-gated potassium channels, myelin-associated molecules, adhesion molecules. Synaptosome analysis further specific molecules collagen, ribosome, solute carrier, receptor families at formed along neurons. By integrating protein data, defined clusters co-regulated neurofilament transporter mRNAs, found subsets mRNA-protein pairs strong correlation anti-correlation in abundance variation. Our findings comprise a rich resource on landscape hippocampus its is accessible syndive.org , highlight coordinated organization between regions, compartments, synapses.

Language: Английский

Citations

1
Levetiracetam prevents Aβ42 production through SV2a-dependent modulation of App processing in Alzheimer's disease models DOI Creative Commons
Nalini R. Rao,

Olivia DeGulis,

Toshihiro Nomura

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 28, 2024

Abstract In Alzheimer’s disease (AD), amyloid-beta (Aβ) peptides are produced by proteolytic cleavage of the amyloid precursor protein (APP), which can occur during synaptic vesicle (SV) cycling at presynapses. Precisely how amyloidogenic APP processing may impair presynaptic proteostasis and to therapeutically target this process remains poorly understood. Using App knock-in mouse models early Aβ pathology, we found proteins with hampered degradation accumulate sites. At mild pathological stage, leads accumulation 42 inside SVs. To explore if targeting SVs modulates accumulation, investigated levetiracetam (Lev), a SV-binding small molecule drug that has shown promise in mitigating AD-related pathologies despite its mechanism action being unclear. We discovered Lev reduces levels decreasing SV2a-dependent manner. corrects SV cycling, results increased surface localization APP, where it favors via non-amyloidogenic pathway. metabolic stable isotopes mass spectrometry confirmed prevents production vivo. transgenic mice aggressive electrophysiological immunofluorescent microscopy analyses revealed treatment minimizes synapse loss. Finally, human Down syndrome brains have elevated proteins, confirming comparable deficit brains. Taken together, report highlights therapeutic potential modify stages AD represent promising strategy prevent pathology before irreversible damage occurs. One Sentence Summary modulating alters thus processing, highlighting for AD.

Language: Английский

Citations

1
Keratinocyte-derived extracellular vesicles in painful diabetic neuropathy DOI Creative Commons
James S. Coy-Dibley,

Nirupa D. Jayaraj,

Dongjun Ren

et al.

Neurobiology of Pain, Journal Year: 2024, Volume and Issue: 17, P. 100176 - 100176

Published: Dec. 17, 2024

Language: Английский

Citations

0
Effect of Porcine Oviductal Fluid-Derived Extracellular Vesicle Supplementation on in Vitro Embryonic Developmental Competence and the Production Efficiency of Cloned Pigs DOI
Jun-Hyeong Kim, Joohyun Shim, Nayoung Ko

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

0