Abstract
Age-dependent progressive neurodegeneration and associated cognitive dysfunction represent a serious concern worldwide. Currently, dementia accounts for the fifth highest cause of death, among which Alzheimer’s disease (AD) represents more than 60% of the cases. AD is associated with progressive cognitive dysfunction which affects daily life of the affected individual and associated family. The cognitive dysfunctions are at least partially due to the degeneration of a specific set of neurons (cholinergic neurons) whose cell bodies are situated in the basal forebrain region (basal forebrain cholinergic neurons, BFCNs) but innervate wide areas of the brain. It has been explicitly shown that the delivery of the neurotrophic protein nerve growth factor (NGF) can rescue BFCNs and restore cognitive dysfunction, making NGF interesting as a potential therapeutic substance for AD. Unfortunately, NGF cannot pass through the blood-brain barrier (BBB) and thus peripheral administration of NGF protein is not viable therapeutically. NGF must be delivered in a way which will allow its brain penetration and availability to the BFCNs to modulate BFCN activity and viability. Over the past few decades, various methodologies have been developed to deliver NGF to the brain tissue. In this chapter, NGF delivery methods are discussed in the context of AD.
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Abbreviations
- Aβ:
-
Amyloid-beta
- AD:
-
Alzheimer’s disease
- APP:
-
Amyloid precursor protein
- BBB:
-
Blood-brain barrier
- BFCN:
-
Basal forebrain cholinergic neuron
- CSF:
-
Cerebrospinal fluid
- ECB:
-
Encapsulated cell biodelivery
- EEG:
-
Electroencephalography
- FTD:
-
Frontotemporal dementia
- HIBI:
-
Hypoxic-ischemic brain injuries
- ICD:
-
Intracerebral delivery
- ICVD:
-
Intracerebroventricular delivery
- MMP3/9:
-
Matrix metalloproteinase 3/9
- mNGF:
-
Mature-NGF
- MSCs:
-
Mesenchymal stem cells
- nbM:
-
Nucleus basalis of Meynert
- NGF:
-
Nerve growth factor
- NGFR:
-
NGF receptor
- NSCs:
-
Neural stem cells
- p75:
-
Low-affinity NGF receptor or LNGFR, or p75 neurotrophin receptor, or p75NTR
- PLGA:
-
Poly(lactic-co-glycolic acid)
- proNGF:
-
Precursor-NGF
- rh:
-
Recombinant human
- TBI:
-
Traumatic brain injury
- tPA:
-
Tissue plasminogen activator
- TrkA:
-
Tropomyosin receptor kinase A
- uPA:
-
Urokinase plasminogen activation
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Mitra, S. et al. (2021). A Review of Techniques for Biodelivery of Nerve Growth Factor (NGF) to the Brain in Relation to Alzheimer’s Disease. In: Calzà, L., Aloe, L., Giardino, L. (eds) Recent Advances in NGF and Related Molecules. Advances in Experimental Medicine and Biology(), vol 1331. Springer, Cham. https://doi.org/10.1007/978-3-030-74046-7_11
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