Evidence mapPaperPMID 41663815Full record

ReviewBiogerontology2026

Synaptic aging and neurodegeneration: the role of synaptic vesicle dynamics and neurotransmitter imbalance.

Pranay Wal, Abhijit Dutta, Talha Jawaid, Mujeeb Ur Rahman, Gowri Krishnaperumal, S Renuka Jyothi, Irwanjot Kaur, Shaker Al-Hasnaawei, Aashna Sinha, Laxmidhar Maharana and 6 more

Abstract readReview
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In one paragraph

Review in Biogerontology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Pranay WalPranveer Singh Institute of Technology, Pharmacy, NH-19, Bhauti Road, Kanpur, UP, 209305, India.
Abhijit DuttaRoyal School of Medical and Allied Sciences, The Assam Royal Global University Betkuchi, Guwahati, Assam, India.
Talha JawaidCollege of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Kingdom of Saudi Arabia.
Mujeeb Ur RahmanCollege of Pharmacy, Knowledge University, Kirkuk Road, Erbil, Kurdistan Region of Iraq, 446015, Iraq.
Gowri KrishnaperumalDepartment of Pharmacology, SRM College of Pharmacy, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603 203, India.
S Renuka JyothiDepartment of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
Irwanjot KaurCentre for Research Impact & Outcome, Chitkara University, Rajpura, 140401, Punjab, India.
Shaker Al-HasnaaweiCollege of Pharmacy, the Islamic University, Najaf, Iraq.
Aashna SinhaSchool of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, Uttarakhand, India.
Laxmidhar MaharanaDepartment of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, 751030, India.
Sourav DebnathNIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India.
Pratap Kumar PatraSchool of Pharmacy & Life Sciences, Centurion University of Technology & Management, Bhubaneswar, Odisha, 752050, India.
Hanish Singh Jayasingh ChellammalDepartment of Pharmacology and Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300, Puncak Alam, Selangor, Malaysia. hanishsinghjc@uitm.edu.my.
Lalit Kumar TyagiLloyd Institute of Management and Technology, Plot No. 11, Knowledge Park II, Greater Noida, Uttar Pradesh, 201306, India.
Smitha KumariLloyd Law College, Plot No. 11, Knowledge Park II, Greater Noida, Uttar Pradesh, 201306, India.
Amin GasmiSociété Francophone de Nutrithérapie Et de Nutrigénétique Appliquée, Villeurbanne, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Synaptic aging is a core manifestation of brain aging arising from the convergence of fundamental biological aging processes, including genomic instability, loss of proteostasis, mitochondrial dysfunction, oxidative stress, and chronic low-grade inflammation. As highly energy-dependent and protein-rich sites of neuronal communication, synapses are particularly vulnerable to age-associated molecular stress. Accumulating evidence indicates that age-related impairments in synaptic vesicle trafficking, recycling, and neurotransmitter homeostasis precede neuronal loss and represent early drivers of cognitive decline and neurodegeneration. Disruption of vesicle dynamics compromises neurotransmitter release, synaptic plasticity, and circuit stability, thereby accelerating synaptic failure. Dysregulation of key neurotransmitter systems, including acetylcholine, dopamine, glutamate, and γ-aminobutyric acid, further exacerbates synaptic dysfunction and cognitive impairment. These changes are driven by interconnected aging mechanisms, wherein impaired proteostasis promotes the accumulation of dysfunctional synaptic proteins, mitochondrial dysfunction limits ATP availability for vesicle mobilisation, and persistent neuroinflammation heightens synaptic vulnerability. Emerging evidence also implicates age-related blood-brain barrier disruption and gut-brain axis dysregulation as additional modulators of synaptic integrity via immune, metabolic, and neurochemical pathways. This review synthesises recent advances in understanding the molecular mechanisms of synaptic aging, with a focus on vesicle dynamics and neurotransmitter imbalance, and discusses therapeutic strategies aimed at enhancing synaptic resilience to promote healthy brain aging.

Indexed as

AgingNeurodegenerative DiseasesNeurotransmitter AgentsSynapsesSynaptic VesiclesAnimalsBrainHumansNeuronal PlasticitySynaptic TransmissionNeurotransmitter AgentsNeurodegenerationNeurotransmitter imbalancePresynaptic dysfunctionSynaptic agingVesicle dynamics

Identifiers

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.