Early Molecular Markers of Neurodegeneration
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".
Deadline for manuscript submissions: 31 March 2026
Special Issue Editors
Interests: neuronal plasticity; dendritic plasticity; synapses
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Interests: mental health; Parkinson’s disease; multiple sclerosis; Alzheimer’s disease; addiction; amyotrophic lateral sclerosis
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Special Issue Information
Dear Colleagues,
While extensive literature describes neuropathologies associated with neuronal and synaptic loss, studies focusing on early diagnosis remain limited. This gap arises because prodromal symptoms in both human and animal models are subtle or clinically silent, eluding detection by standard behavioral assessments and cognitive tests.
Once overt cognitive impairment manifests, pathologies progress rapidly and respond poorly to available therapies. Neural circuits lost by this stage cannot be restored, even if further degeneration is slowed. These factors underscore the critical importance of identifying neurodegenerative processes at their earliest, preclinical stages.
Notable early diagnostic markers include the following:
- Synaptic alterations preceding deafferentation, such as elevated cerebrospinal fluid levels of neurogranin, SNAP-25, synaptotagmin-1, and GAP-43; neuron-derived exosomes; and dysregulation of long-term synaptic signaling pathways (voltage-gated calcium channels, metabotropic receptors, scaffolding proteins, mTOR signaling).
- Dysregulation of intracellular biochemical cascades, including transcription factor activity, nitric oxide synthase signaling, mitochondrial dysfunction, and altered mitochondria–endoplasmic reticulum contact sites.
- Reactive glial phenotypes—proinflammatory astrocytes and activated microglia—mediated by TLR4 and P2X7 receptors and the JAK–STAT3 pathway; synaptic clearance via receptor-mediated engulfment (MEGF10, MERTK).
- Ultrastructural morphological changes in neuronal and glial cells detectable by advanced electron microscopy.
- Subtle behavioral abnormalities not captured by conventional cognitive assessments.
This Special Issue highlights these and other emerging approaches for the early diagnosis of neurodegeneration.
Dr. Eduard Korkotian
Prof. Dr. Michele Papa
Guest Editors
Manuscript Submission Information
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Keywords
- neuronal loss
- synaptic loss
- synaptic alterations
- exosomes
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