Neurotrophic Factors in Alzheimer's Disease Therapeutics

Neurotrophic factors are a class of proteins that support neuronal survival, differentiation and synaptic plasticity, and their dysregulation is intimately linked to the pathogenesis of Alzheimer’s disease. Among these, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and other members of the neurotrophin family play central roles in preserving hippocampal circuitry and cognitive function. In Alzheimer’s disease, reductions in neurotrophic support contribute to synaptic loss, aberrant amyloid-β aggregation and tau hyperphosphorylation, thereby accelerating neurodegeneration. Therapeutic strategies under investigation include gene therapy to augment endogenous neurotrophin expression, peptide or small-molecule mimetics that activate high-affinity receptors, and novel delivery systems capable of crossing the blood–brain barrier. Advances in understanding receptor-mediated signalling cascades—such as TrkB-dependent activation of ERK, PI3K/Akt and CREB pathways—have informed the design of targeted interventions. Emerging approaches also combine neurotrophic enhancement with modulation of neuroinflammation and amyloid clearance, aiming to restore functional neuronal networks and slow cognitive decline.

Research from Nature Portfolio

Recent studies have demonstrated that systemic delivery of a fusion peptide combining the active domain of BDNF with a cell-penetrating motif can efficiently cross the blood–brain barrier and engage TrkB receptors in rodent models of Alzheimer’s-like pathology. Intraperitoneal administration of this peptide activated downstream ERK1/2 and Akt signalling, restored levels of memory-associated proteins and improved spatial learning performance. Moreover, treatment modulated both amyloid and tau pathology and influenced cholinergic markers, underlining the potential of peripherally administered neurotrophic agonists to target multiple pathological cascades in vivo.

Neurotrophic Factors in Alzheimer's Disease Therapeutics publication trend

The graph below shows the total number of articles in neurotrophic factors in alzheimer's disease therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Neurotrophic factor: A protein that promotes growth, survival and maintenance of neurons.

Brain-derived neurotrophic factor (BDNF): A key neurotrophin involved in synaptic plasticity and cognitive function.

TrkB receptor: A high-affinity receptor tyrosine kinase for BDNF that activates ERK, PI3K/Akt and other pathways.

Synaptic plasticity: The ability of synapses to strengthen or weaken in response to activity, critical for learning and memory.

Amyloid-β: A peptide that aggregates to form plaques and disrupts neuronal function in Alzheimer’s disease.

Tauopathy: A class of neurodegenerative disorders characterised by accumulation of hyperphosphorylated tau protein.

References

1. Intraperitoneal Administration of a Novel TAT-BDNF Peptide Ameliorates Cognitive Impairments via Modulating Multiple Pathways in Two Alzheimer’s Rodent Models. Scientific Reports (2015).
2. Lactobacillus-derived extracellular vesicles counteract Aβ42-induced abnormal transcriptional changes through the upregulation of MeCP2 and Sirt1 and improve Aβ pathology in Tg-APP/PS1 mice. Experimental & Molecular Medicine (2023).
3. Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer’s Disease Neurodegeneration. Cells (2023).
4. Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential. Translational Neurodegeneration (2022).