Proteomic mapping of Drosophila transgenic elav.L-GAL4/+ brain as a tool to illuminate neuropathology mechanisms

Velentzas, Athanassios D.; Katarachia, Stamatia A.; Sagioglou, Niki E.; Tsioka, Maria M.; Anagnostopoulos, Athanasios K.; Mpakou, Vassiliki; Theotoki, Eleni I.; Giannopoulou, Aikaterini F.; Keramaris, K.E.; Papassideri, Issidora S.; Tsangaris, George Th.; Stravopodis, Dimitrios J.

doi:10.1038/s41598-020-62510-0

Cited by 3 publications

(1 citation statement)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6A,B ). Proteasomal activity is known to decline with age in humans 39 , and its beneficial impact on lifespan has been extensively documented, exemplified by human bone marrow multipotent stromal cells 40 or Drosophila 41 models. Also consistent with observations in T cells ( Figs.…”

Section: Discussionmentioning

confidence: 99%

Unveiling the crucial neuronal role of the proteasomal ATPase subunit genePSMC5in neurodevelopmental proteasomopathies

Küry,

Stanton,

van Woerden

et al. 2024

Preprint

View full text Add to dashboard Cite

Neurodevelopmental proteasomopathies have recently emerged as a distinct class of neurodevelopmental disorders (NDD). These conditions involve alterations in genes of the 26S proteasome, a protein complex essential for maintaining protein homeostasis in eukaryotic cells. Our study identified 23 unique variants in PSMC5, which encodes the AAA-ATPase proteasome subunit PSMC5/Rpt6, causing syndromic NDD in 38 unrelated individuals. PSMC5 loss-of-function resulted in abnormal protein aggregation, profoundly affecting innate immune signaling, mitophagy rate, and lipid metabolism in samples of affected individuals samples. Moreover, the morphology of human hippocampal neurons was altered by overexpression of PSMC5 variants, while PSMC5 knockdown led to impaired reversal learning in flies and loss of excitatory synapses in rat hippocampal neurons. Promisingly, targeting key integrated stress response components like PKR and GCN2 kinases alleviated immune alterations in cells of affected individuals. These findings deepen our understanding of the molecular mechanisms underlying neurodevelopmental proteasomopathies and link these disorders with neurodegenerative disease research.

show abstract

Section: Discussionmentioning

confidence: 99%

Unveiling the crucial neuronal role of the proteasomal ATPase subunit genePSMC5in neurodevelopmental proteasomopathies

Küry,

Stanton,

van Woerden

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aβ42-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach

et al. 2022

View full text Add to dashboard Cite

Accumulation of Aβ 42 peptides forming plaque in various regions of the brain is a hallmark of Alzheimer's disease (AD) progression. However, to date, there is no effective management strategy reported for attenuation of Aβ 42 induced toxicity in the early stages of the disease. Alternate medicinal systems such as Ayurveda in the past few decades show promising results in the management of neuronal complications. Medhya Rasayana such as Brahmi is known for its neuroprotective properties via resolving memory-related issues, while the underlying molecular mechanism of the same remains unclear. In the present study, we aimed to understand the neuroprotective effects of the aqueous extract of Bacopa monnieri and Centella asiatica (commonly known as Brahmi) against the Aβ 42 expressing model of the Drosophila melanogaster. By applying a quantitative proteomics approach, the study identi ed > 90% of differentially expressed proteins from Aβ 42 expressing D. melanogaster were either restored to their original expression pattern or showed no change in expression pattern upon receiving either Brahmi extract treatment. The Brahmi restored proteins were part of neuronal pathways associated with cell cycle re-entry, apoptosis, and mitochondrial dynamics. The neuroprotective effect of Brahmi was also validated by negative geotaxis behavioral analysis suggesting its protective role against behavioral de cits exerted by Aβ 42 toxicity. We believe that these discoveries will provide a platform for developing novel therapeutics for AD management by deciphering molecular targets of neuroprotection conferred by an aqueous extract of Bacopa monnieri or Centella asiatica.

show abstract

Aβ42 Expressing Drosophila melanogaster Model for Alzheimer's Disease: Quantitative Proteomics Identifies Altered Protein Dynamics of Relevance to Neurodegeneration

Deolankar

Najar

Raghu

et al. 2022

OMICS: A Journal of Integrative Biology

View full text Add to dashboard Cite

Proteomic mapping of Drosophila transgenic elav.L-GAL4/+ brain as a tool to illuminate neuropathology mechanisms

Cited by 3 publications

References 111 publications

Unveiling the crucial neuronal role of the proteasomal ATPase subunit genePSMC5in neurodevelopmental proteasomopathies

Unveiling the crucial neuronal role of the proteasomal ATPase subunit genePSMC5in neurodevelopmental proteasomopathies

Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aβ42-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach

Aβ42 Expressing Drosophila melanogaster Model for Alzheimer's Disease: Quantitative Proteomics Identifies Altered Protein Dynamics of Relevance to Neurodegeneration

Contact Info

Product

Resources

About