Therapeutic potential of nasal kisspeptin-54 for reducing α-synuclein accumulation and restoring hippocampal synaptic plasticity in a 6-hydroxydopamine-induced rat model of Parkinson's disease.

Gemici Sinen A, Savran E, Güleç OB, Sinen O, Derin N

Turkish journal of medical sciences19 Jun 2026

PMID42676968PMCIDPMC13528715DOI10.55730/1300-0144.6376PepBankPUB-42676968

Summary

Background/aimParkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons and pathological aggregation of α-synuclein (α-syn), leading to significant motor and cognitive impairments. Kisspeptin-54 (KP-54), a neuropeptide primarily involved in reproductive regulation, has recently been implicated in neurorestorative processes, with emerging evidence suggesting beneficial effects on locomotor activity and cognitive function. However, its therapeutic potential in PD has not yet been fully investigated. This study aimed to evaluate the therapeutic efficacy of chronic nasal KP-54 administration in a 6-hydroxydopamine (6-OHDA) rat model of PD, focusing on motor and cognitive outcomes, hippocampal synaptic plasticity, and α-syn pathology.Materials and methodsAdult Sprague-Dawley rats underwent unilateral 6-OHDA injections into the medial forebrain bundle to induce dopaminergic degeneration. Beginning 3 weeks after lesion induction, animals received daily nasal KP-54 or vehicle treatment for an additional 3 weeks. Motor performance was assessed using the catalepsy, beam balance, and open field tests, whereas cognitive function was evaluated using the Y-maze and object location test. Baseline assessments were conducted on day 0 prior to lesion formation. Electrophysiological recordings obtained from the hippocampal CA1 region were used to assess synaptic plasticity. Dopaminergic neuron survival and α-syn accumulation in the substantia nigra and hippocampus were quantified by immunofluorescence analysis.ResultsChronic nasal KP-54 significantly ameliorated motor and cognitive deficits induced by 6-OHDA. KP-54 restored hippocampal synaptic plasticity, enhanced the survival of tyrosine hydroxylase-positive dopaminergic neurons, and reduced α-syn accumulation in both the substantia nigra and hippocampus.ConclusionThe findings indicate that nasal KP-54 administration exerts neurorestorative effects in a 6-OHDA rat model of PD by preserving dopaminergic neurons, improving synaptic function, and attenuating pathological α-syn aggregation. These results position KP-54 as a promising candidate for disease-modifying therapy in Parkinson's disease.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

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

01AnimalAnimal study (in vivo)Efficacy outcome
In 6-OHDA rats, chronic nasal KP-54 ameliorated motor deficits compared with vehicle.
In plain wordsIn rats with a Parkinson's disease model, nasal KP-54 improved movement problems compared with vehicle.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreaseMotor performance
Study
ratn: not reported in source
6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease
Comparator
Vehicle
Outcome group
Exercise and physical function · Nervous system and cognition
Studied dose
Dose not stated · nasal · 3 weeksAs given in this study (rat).
Source sentences
Summary
Chronic nasal KP-54 significantly ameliorated motor
3 context sentences(design, population, supporting numbers)
Summary · context
KP-54 significantly ameliorated motor and cognitive deficits induced by 6-OHDA
Summary · context
Adult Sprague-Dawley rats underwent unilateral 6-OHDA injections into the medial forebrain bundle to induce dopaminergic degeneration.
Summary · context
Beginning 3 weeks after lesion induction, animals received daily nasal KP-54 or vehicle treatment for an additional 3 weeks.
Show in the study text Report a problemFND-4267696801
02AnimalAnimal study (in vivo)Efficacy outcome
In 6-OHDA rats, chronic nasal KP-54 ameliorated cognitive deficits compared with vehicle.
In plain wordsIn rats with a Parkinson's disease model, nasal KP-54 improved thinking and memory problems compared with vehicle.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreaseCognitive performance
Study
ratn: not reported in source
6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease
Comparator
Vehicle
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated · nasal · 3 weeksAs given in this study (rat).
Source sentences
Summary
Chronic nasal KP-54 significantly ameliorated motor and cognitive deficits induced by 6-OHDA.
2 context sentences(design, population, supporting numbers)
Summary · context
Adult Sprague-Dawley rats underwent unilateral 6-OHDA injections into the medial forebrain bundle to induce dopaminergic degeneration.
Summary · context
Beginning 3 weeks after lesion induction, animals received daily nasal KP-54 or vehicle treatment for an additional 3 weeks.
Show in the study text Report a problemFND-4267696802
03AnimalAnimal study (in vivo)Efficacy outcome
In 6-OHDA rats, KP-54 restored hippocampal synaptic plasticity.
In plain wordsIn rats with a Parkinson's disease model, KP-54 restored a measure of brain connection function in the hippocampus.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreaseHippocampal synaptic plasticity
Study
ratn: not reported in source
6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease
Comparator
Vehicle
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated · nasal · 3 weeksAs given in this study (rat).
Source sentences
Summary
KP-54 restored hippocampal synaptic plasticity
2 context sentences(design, population, supporting numbers)
Summary · context
Adult Sprague-Dawley rats underwent unilateral 6-OHDA injections into the medial forebrain bundle to induce dopaminergic degeneration.
Summary · context
Beginning 3 weeks after lesion induction, animals received daily nasal KP-54 or vehicle treatment for an additional 3 weeks.
Show in the study text Report a problemFND-4267696803
04AnimalAnimal study (in vivo)Efficacy outcome
In 6-OHDA rats, KP-54 enhanced the survival of tyrosine hydroxylase-positive dopaminergic neurons.
In plain wordsIn rats with a Parkinson's disease model, KP-54 helped more dopamine-producing nerve cells survive.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreaseSurvival of tyrosine hydroxylase-positive dopaminergic neurons
Study
ratn: not reported in source
6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease
Comparator
Vehicle
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · nasal · 3 weeksAs given in this study (rat).
Source sentences
Summary
enhanced the survival of tyrosine hydroxylase-positive dopaminergic neurons
2 context sentences(design, population, supporting numbers)
Summary · context
Adult Sprague-Dawley rats underwent unilateral 6-OHDA injections into the medial forebrain bundle to induce dopaminergic degeneration.
Summary · context
Beginning 3 weeks after lesion induction, animals received daily nasal KP-54 or vehicle treatment for an additional 3 weeks.
Show in the study text Report a problemFND-4267696804
05AnimalAnimal study (in vivo)Efficacy outcome
In 6-OHDA rats, KP-54 reduced α-synuclein accumulation in the substantia nigra.
In plain wordsIn rats with a Parkinson's disease model, KP-54 lowered build-up of the α-synuclein protein in the substantia nigra.
Peptide
Kisspeptin-54 (metastin)
Outcome
Decreaseα-Synuclein accumulation in the substantia nigra
Study
ratn: not reported in source
6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease
Comparator
Vehicle
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · nasal · 3 weeksAs given in this study (rat).
Source sentences
Summary
reduced α-syn accumulation in both the substantia nigra and hippocampus.
2 context sentences(design, population, supporting numbers)
Summary · context
Adult Sprague-Dawley rats underwent unilateral 6-OHDA injections into the medial forebrain bundle to induce dopaminergic degeneration.
Summary · context
Beginning 3 weeks after lesion induction, animals received daily nasal KP-54 or vehicle treatment for an additional 3 weeks.
Show in the study text Report a problemFND-4267696805
06AnimalAnimal study (in vivo)Efficacy outcome
In 6-OHDA rats, KP-54 reduced α-synuclein accumulation in the hippocampus.
In plain wordsIn rats with a Parkinson's disease model, KP-54 lowered build-up of the α-synuclein protein in the hippocampus.
Peptide
Kisspeptin-54 (metastin)
Outcome
Decreaseα-Synuclein accumulation in the hippocampus
Study
ratn: not reported in source
6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease
Comparator
Vehicle
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · nasal · 3 weeksAs given in this study (rat).
Source sentences
Summary
reduced α-syn accumulation in both the substantia nigra and hippocampus.
2 context sentences(design, population, supporting numbers)
Summary · context
Adult Sprague-Dawley rats underwent unilateral 6-OHDA injections into the medial forebrain bundle to induce dopaminergic degeneration.
Summary · context
Beginning 3 weeks after lesion induction, animals received daily nasal KP-54 or vehicle treatment for an additional 3 weeks.
Show in the study text Report a problemFND-4267696806

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.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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