Neurotrophic Factors in Neurodegeneration

Overview

Journal Brain Pathol

Date 2006 Nov 17

PMID 17107599

Citations 25

Authors

Armin Blesch

Affiliations

Soon will be listed here.

Abstract

Neurotrophic factors (NTFs) have the unique potential to support neuronal survival and to augment neuronal function in the injured and diseased nervous system. Numerous studies conducted over the last 20 years have provided evidence for the potent therapeutic potential of NTFs in animal models of neurodegenerative diseases. However, major obstacles for the therapeutic use of NTFs are the inability to deliver proteins across the blood-brain-barrier, and dose-limiting adverse effects resulting from the broad exposure of nontargeted structures to NTFs. Two recent developments have allowed NTFs' promise to be truly tested for the first time: first, recent improvements in viral vectors that allow the targeted delivery of NTFs while providing a long-lasting supply and sufficient therapeutic doses of NTFs; and second, improved animal models developed in recent years. In this review, we will discuss some of the potential therapeutic applications of NTFs in neurodegenerative diseases and the potential contribution of disturbed neurotrophic factor signaling to neurodegenerative diseases.

Citing Articles

Neurotrophin-3 Rescues Striatal Synaptic Plasticity in Model of Neurodegeneration by PLC Signaling Activation.

Gomez-Pineda V, Nieto-Mendoza E, Torres-Cruz F, Hernandez-Echeagaray E CNS Neurol Disord Drug Targets. 2024; 23(12):1488-1498.

PMID: 38859788 DOI: 10.2174/0118715273298919240531110022.

Novel Gene Therapy Approaches for Targeting Neurodegenerative Disorders: Focusing on Delivering Neurotrophic Genes.

Kumari S, Kamiya A, Karnik S, Rohilla S, Dubey S, Taliyan R Mol Neurobiol. 2024; 62(1):386-411.

PMID: 38856793 DOI: 10.1007/s12035-024-04260-y.

Tremendous Fidelity of Vitamin D3 in Age-related Neurological Disorders.

Skv M, Abraham S, Eshwari O, Golla K, Jhelum P, Maity S Mol Neurobiol. 2024; 61(9):7211-7238.

PMID: 38372958 DOI: 10.1007/s12035-024-03989-w.

Potential Therapeutic Approach using Aromatic l-amino Acid Decarboxylase and Glial-derived Neurotrophic Factor Therapy Targeting Putamen in Parkinson's Disease.

Tripathi R, Goyal L, Singh S Curr Gene Ther. 2024; 24(4):278-291.

PMID: 38310455 DOI: 10.2174/0115665232283842240102073002.

Advancing Alzheimer's Therapeutics: Exploring the Impact of Physical Exercise in Animal Models and Patients.

Andrade-Guerrero J, Rodriguez-Arellano P, Barron-Leon N, Orta-Salazar E, Ledesma-Alonso C, Diaz-Cintra S Cells. 2023; 12(21).

PMID: 37947609 PMC: 10648553. DOI: 10.3390/cells12212531.

References

Perry E, Perry R, Blessed G, Tomlinson B . Necropsy evidence of central cholinergic deficits in senile dementia. Lancet. 1977; 1(8004):189. DOI: 10.1016/s0140-6736(77)91780-9. View

Olson L, Nordberg A, von Holst H, Backman L, Ebendal T, Alafuzoff I . Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report). J Neural Transm Park Dis Dement Sect. 1992; 4(1):79-95. DOI: 10.1007/BF02257624. View

Ikeda K, Wong V, Holmlund T, Greene T, Cedarbaum J, Lindsay R . Histometric effects of ciliary neurotrophic factor in wobbler mouse motor neuron disease. Ann Neurol. 1995; 37(1):47-54. DOI: 10.1002/ana.410370110. View

Wang L, Lu Y, Muramatsu S, Ikeguchi K, Fujimoto K, Okada T . Neuroprotective effects of glial cell line-derived neurotrophic factor mediated by an adeno-associated virus vector in a transgenic animal model of amyotrophic lateral sclerosis. J Neurosci. 2002; 22(16):6920-8. PMC: 6757879. DOI: 20026668. View

Wu K, Meyer E, Bennett J, Meyers C, Hughes J, King M . AAV2/5-mediated NGF gene delivery protects septal cholinergic neurons following axotomy. Brain Res. 2005; 1061(2):107-13. DOI: 10.1016/j.brainres.2005.08.056. View

Holtzman D, Li Y, Chen K, Gage F, Epstein C, Mobley W . Nerve growth factor reverses neuronal atrophy in a Down syndrome model of age-related neurodegeneration. Neurology. 1993; 43(12):2668-73. DOI: 10.1212/wnl.43.12.2668. View

Koliatsos V, Clatterbuck R, Winslow J, Cayouette M, Price D . Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron. 1993; 10(3):359-67. DOI: 10.1016/0896-6273(93)90326-m. View

Eriksdotter Jonhagen M, Nordberg A, Amberla K, Backman L, Ebendal T, Meyerson B . Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 1998; 9(5):246-57. DOI: 10.1159/000017069. View

Hyman C, Hofer M, Barde Y, Juhasz M, Yancopoulos G, Squinto S . BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature. 1991; 350(6315):230-2. DOI: 10.1038/350230a0. View

10.

Sahenk Z . Neurotrophins and peripheral neuropathies. Brain Pathol. 2006; 16(4):311-9. PMC: 8096058. DOI: 10.1111/j.1750-3639.2006.00038.x. View

11.

Kordower J, Isacson O, Emerich D . Cellular delivery of trophic factors for the treatment of Huntington's disease: is neuroprotection possible?. Exp Neurol. 1999; 159(1):4-20. DOI: 10.1006/exnr.1999.7156. View

12.

Emerich D, Winn S, Hantraye P, Peschanski M, Chen E, Chu Y . Protective effect of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington's disease. Nature. 1997; 386(6623):395-9. DOI: 10.1038/386395a0. View

13.

Markowska A, Price D, Koliatsos V . Selective effects of nerve growth factor on spatial recent memory as assessed by a delayed nonmatching-to-position task in the water maze. J Neurosci. 1996; 16(10):3541-8. PMC: 6579126. View

14.

Canals J, Pineda J, Torres-Peraza J, Bosch M, Martin-Ibanez R, Teresa Munoz M . Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease. J Neurosci. 2004; 24(35):7727-39. PMC: 6729627. DOI: 10.1523/JNEUROSCI.1197-04.2004. View

15.

Yan Q, Elliott J, Snider W . Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature. 1992; 360(6406):753-5. DOI: 10.1038/360753a0. View

16.

Klein R, Muir D, King M, Peel A, Zolotukhin S, Moller J . Long-term actions of vector-derived nerve growth factor or brain-derived neurotrophic factor on choline acetyltransferase and Trk receptor levels in the adult rat basal forebrain. Neuroscience. 1999; 90(3):815-21. DOI: 10.1016/s0306-4522(98)00537-5. View

17.

Martinez-Serrano A, Fischer W, Bjorklund A . Reversal of age-dependent cognitive impairments and cholinergic neuron atrophy by NGF-secreting neural progenitors grafted to the basal forebrain. Neuron. 1995; 15(2):473-84. DOI: 10.1016/0896-6273(95)90051-9. View

18.

Milbrandt J, de Sauvage F, Fahrner T, Baloh R, Leitner M, Tansey M . Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron. 1998; 20(2):245-53. DOI: 10.1016/s0896-6273(00)80453-5. View

19.

Tuszynski M, Thal L, Pay M, Salmon D, U H, Bakay R . A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med. 2005; 11(5):551-5. DOI: 10.1038/nm1239. View

20.

Araujo D, Hilt D . Glial cell line-derived neurotrophic factor attenuates the excitotoxin-induced behavioral and neurochemical deficits in a rodent model of Huntington's disease. Neuroscience. 1997; 81(4):1099-110. DOI: 10.1016/s0306-4522(97)00079-1. View