Evidence map›Paper›PMID 40430064›Full record

ReviewInternational journal of molecular sciences2025

BDNF/proBDNF Interplay in the Mediation of Neuronal Apoptotic Mechanisms in Neurodegenerative Diseases.

Marina Mitrovic, Dragica Selakovic, Nemanja Jovicic, Biljana Ljujic, Gvozden Rosic

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–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

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  10. BDNF-amyloid-Frontiers in molecular neuroscience · 2026
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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

5 authors.

Marina MitrovicDepartment of Medical Biochemistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
Dragica SelakovicDepartment of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.ORCID 0000-0001-8264-2477
Nemanja JovicicDepartment of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.ORCID 0000-0003-1697-8380
Biljana LjujicDepartment of Genetics, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
Gvozden RosicDepartment of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The neurotrophic system includes neurotrophins, such as brain-derived neurotrophic factor (BDNF) and its precursor proBDNF, which play conflicting roles in neuronal survival and apoptosis, with their balance having a significant impact on neurodegenerative outcomes. While BDNF is widely acknowledged as a potent neurotrophin that promotes neuronal survival and differentiation, its precursor, proBDNF, has the opposite effect, promoting apoptosis and neuronal death. This review highlights the new and unique aspects of BDNF/proBDNF interaction in the modulation of neuronal apoptotic pathways in neurodegenerative disorders. It systematically discusses the cross-talk in apoptotic signaling at the molecular level, whereby BDNF activates survival pathways such as PI3K/Akt and MAPK/ERK, whereas proBDNF activates p75NTR and sortilin to induce neuronal apoptosis via JNK, RhoA, NFkB, and Rac-GTPase pathways such as caspase activation and mitochondrial injury. Moreover, this review emphasizes the factors that affect the balance between proBDNF and BDNF levels within the context of neurodegeneration, including proteolytic processing, the expression of TrkB and p75NTR receptors, and extrinsic gene transcription regulators. Cellular injury, stress, or signaling pathway alterations can disrupt the balance of BDNF/proBDNF, which may be involved in apoptotic-related neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's diseases. This review provides a comprehensive framework for targeting neurotrophin signaling in the development of innovative therapies for neuronal survival and managing apoptotic-related neurodegenerative disorders, addressing the mechanistic complexity and clinical feasibility of BDNF/proBDNF interaction.

Indexed as

ApoptosisBrain-Derived Neurotrophic FactorNeurodegenerative DiseasesNeuronsProtein PrecursorsAnimalsHumansSignal TransductionBDNF protein, humanBrain-Derived Neurotrophic FactorProtein PrecursorsAlzheimer’s diseaseapoptosisHuntington’s diseaseneurotrophin receptorsneurotrophinsParkinson’s disease

Identifiers

PMID40430064
PMCPMC12112594

What OpenQuestion holds

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Registered trials

None linked

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 OpenQuestion graph.