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Study · In vitro (cells) · 2022

4 results

Kisspeptin-10 Rescues Cholinergic Differentiated SHSY-5Y Cells from α-Synuclein-Induced Toxicity In Vitro.

Simon C, Soga T, Ahemad N, Bhuvanendran S, Parhar I

International journal of molecular sciences6 May 2022Cited by 9 (Europe PMC)

PMID35563582 (opens in a new tab)PMCIDPMC9105316 (opens in a new tab)DOI10.3390/ijms23095193 (opens in a new tab)PepBankPUB-35563582
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Summary

The neuropathological substrate of dementia with Lewy bodies (DLB) is defined by the inextricable cross-seeding accretion of amyloid-β (Aβ) and α-synuclein (α-syn)-laden deposits in cholinergic neurons. The recent revelation that neuropeptide kisspeptin-10 (KP-10) is able to mitigate Aβ toxicity via an extracellular binding mechanism may provide a new horizon for innovative drug design endeavors. Considering the sequence similarities between α-syn's non-amyloid-β component (NAC) and Aβ's C-terminus, we hypothesized that KP-10 would enhance cholinergic neuronal resistance against α-syn's deleterious consequences through preferential binding. Here, human cholinergic SH-SY5Y cells were transiently transformed to upsurge the mRNA expression of α-syn while α-syn-mediated cholinergic toxicity was quantified utilizing a standardized viability-based assay. Remarkably, the E46K mutant α-syn displayed elevated α-syn mRNA levels, which subsequently induced more cellular toxicity compared with the wild-type α-syn in choline acetyltransferase (ChAT)-positive cholinergic neurons. Treatment with a high concentration of KP-10 (10 µM) further decreased cholinergic cell viability, while low concentrations of KP-10 (0.01-1 µM) substantially suppressed wild-type and E46K mutant α-syn-mediated toxicity. Correlating with the in vitro observations are approximations from in silico algorithms, which inferred that KP-10 binds favorably to the C-terminal residues of wild-type and E46K mutant α-syn with CDOCKER energy scores of -118.049 kcal/mol and -114.869 kcal/mol, respectively. Over the course of 50 ns simulation time, explicit-solvent molecular dynamics conjointly revealed that the docked complexes were relatively stable despite small-scale fluctuations upon assembly. Taken together, our findings insinuate that KP-10 may serve as a novel therapeutic scaffold with far-reaching implications for the conceptualization of α-syn-based treatments.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Safety outcome

    In human cholinergic SH-SY5Y cells, a high concentration of kisspeptin‑10 (10 µM) further decreased cell viability.

    In plain wordsIn cells, a high concentration of kisspeptin‑10 lowered the survival of nerve-like cells further.

    Peptide
    Kisspeptin-10
    Outcome
    DecreaseCholinergic cell viability at 10 µM
    Study

    humann: not reported in source

    human cholinergic SH-SY5Y cells expressing α-synuclein
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    10 µMAs given in this study (human).

    Source sentences

    Summary
    Treatment with a high concentration of KP-10 (10 µM) further decreased cholinergic cell viability
    1 context sentence
    Summary · context
    Here, human cholinergic SH-SY5Y cells were transiently transformed to upsurge the mRNA expression of α-syn while α-syn-mediated cholinergic toxicity was quantified utilizing a standardized viability-based assay.
  2. 02LabIn vitro (cells)Efficacy outcome

    In human cholinergic SH-SY5Y cells, low concentrations of kisspeptin‑10 (0.01-1 µM) substantially suppressed wild-type and E46K mutant α-synuclein toxicity.

    In plain wordsIn cells, low concentrations of kisspeptin‑10 strongly reduced the harm caused by the α-synuclein protein.

    Peptide
    Kisspeptin-10
    Outcome
    Decreaseα-Synuclein-mediated cell toxicity (wild-type and E46K)
    Study

    humann: not reported in source

    human cholinergic SH-SY5Y cells expressing α-synuclein
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    0.01-1 µMAs given in this study (human).

    Measurements

    KP-10 concentration
    0.01 to 1 µM
    SH-SY5Y cells

    Source sentences

    Summary
    low concentrations of KP-10 (0.01-1 µM) substantially suppressed wild-type and E46K mutant α-syn-mediated toxicity.
    1 context sentence
    Summary · context
    Here, human cholinergic SH-SY5Y cells were transiently transformed to upsurge the mRNA expression of α-syn while α-syn-mediated cholinergic toxicity was quantified utilizing a standardized viability-based assay.
  3. 03Computer modelIn silicoActivity measurement

    In silico docking predicted that kisspeptin‑10 binds favorably to the C-terminal residues of wild-type and E46K mutant α-synuclein.

    In plain wordsIn computer models, kisspeptin‑10 was predicted to bind well to the α-synuclein protein.

    Peptide
    Kisspeptin-10
    Outcome
    Not applicableDocking energy of KP-10 to α-synuclein C-terminus
    Study

    n: not reported in source

    molecular docking of KP-10 to α-synuclein
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    CDOCKER energy score
    −118.049 kcal/mol
    wild-type α-synuclein
    CDOCKER energy score
    −114.869 kcal/mol
    E46K mutant α-synuclein

    Source sentences

    Summary
    Correlating with the in vitro observations are approximations from in silico algorithms, which inferred that KP-10 binds favorably to the C-terminal residues of wild-type and E46K mutant α-syn with CDOCKER energy scores of -118.049 kcal/mol and -114.869 kcal/mol, respectively.
    1 context sentence
    Summary · context
    Here, human cholinergic SH-SY5Y cells were transiently transformed to upsurge the mRNA expression of α-syn while α-syn-mediated cholinergic toxicity was quantified utilizing a standardized viability-based assay.
  4. 04Computer modelIn silicoActivity measurement

    In 50 ns molecular dynamics simulations, the docked kisspeptin‑10 and α-synuclein complexes were relatively stable.

    In plain wordsIn computer simulations, the kisspeptin‑10 and α-synuclein complexes stayed fairly stable.

    Peptide
    Kisspeptin-10
    Outcome
    Not applicableStability of KP-10 and α-synuclein docked complexes
    Study

    n: not reported in source

    50 ns explicit-solvent molecular dynamics
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Over the course of 50 ns simulation time, explicit-solvent molecular dynamics conjointly revealed that the docked complexes were relatively stable despite small-scale fluctuations upon assembly.
    1 context sentence
    Summary · context
    Here, human cholinergic SH-SY5Y cells were transiently transformed to upsurge the mRNA expression of α-syn while α-syn-mediated cholinergic toxicity was quantified utilizing a standardized viability-based assay.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 09:43 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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