GDNF, NGF and BDNF as therapeutic options for neurodegeneration.

doi:10.1016/J.PHARMTHERA.2013.01.004

Home
/
Papers
/
GDNF, NGF and BDNF as therapeutic options for neurodegeneration.

Journal Article•DOI•

GDNF, NGF and BDNF as therapeutic options for neurodegeneration.

Shelley J Allen, Judy J. Watson, Deborah K. Shoemark, Neil U Barua¹, Nikunj K. Patel¹ - Show less +1 more•Institutions (1)

University of Bristol¹

01 May 2013-Pharmacology & Therapeutics (Pergamon Press)-Vol. 138, Iss: 2, pp 155-175

TL;DR: These neurotrophic factors are evaluated as potential short or long-term treatments, weighing up preclinical and clinical results with the possible effects on the underlying neurodegenerative process.

read less

About: This article is published in Pharmacology & Therapeutics.The article was published on 2013-05-01. It has received 592 citations till now. The article focuses on the topics: Glial cell line-derived neurotrophic factor & Neurotrophic factors.

...read moreread less

Citations

PDF

Open Access

More filters

Journal Article•DOI•

The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma

[...]

Haitao Wang¹, Rikang Wang¹, Thilini Thrimawithana², Peter J. Little², Jiangping Xu³, Zhong-Ping Feng⁴, Wenhua Zheng¹ - Show less +3 more•Institutions (4)

Sun Yat-sen University¹, RMIT University², Southern Medical University³, University of Toronto⁴

31 Aug 2014-BioMed Research International

TL;DR: The current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma are discussed.

...read moreread less

Abstract: Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC's survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.

...read moreread less

365 citations

Cites result from "GDNF, NGF and BDNF as therapeutic o..."

...These results in animals have led to several clinical trials [5, 6]....
[...]

Journal Article•DOI•

Overcoming the Blood-Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases.

[...]

Denzil Furtado¹, Mattias Björnmalm², Mattias Björnmalm¹, Scott Ayton¹, Ashley I. Bush¹, Kristian Kempe³, Frank Caruso¹ - Show less +3 more•Institutions (3)

University of Melbourne¹, Imperial College London², Monash University³

01 Nov 2018-Advanced Materials

TL;DR: The objective is to provide the diverse range of researchers active in the field with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial‐mediated treatment of neurological diseases.

...read moreread less

Abstract: Therapies directed toward the central nervous system remain difficult to translate into improved clinical outcomes. This is largely due to the blood-brain barrier (BBB), arguably the most tightly regulated interface in the human body, which routinely excludes most therapeutics. Advances in the engineering of nanomaterials and their application in biomedicine (i.e., nanomedicine) are enabling new strategies that have the potential to help improve our understanding and treatment of neurological diseases. Herein, the various mechanisms by which therapeutics can be delivered to the brain are examined and key challenges facing translation of this research from benchtop to bedside are highlighted. Following a contextual overview of the BBB anatomy and physiology in both healthy and diseased states, relevant therapeutic strategies for bypassing and crossing the BBB are discussed. The focus here is especially on nanomaterial-based drug delivery systems and the potential of these to overcome the biological challenges imposed by the BBB. Finally, disease-targeting strategies and clearance mechanisms are explored. The objective is to provide the diverse range of researchers active in the field (e.g., material scientists, chemists, engineers, neuroscientists, and clinicians) with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial-mediated treatment of neurological diseases.

...read moreread less

340 citations

Journal Article•DOI•

Astrocytic modulation of blood brain barrier: perspectives on Parkinson’s disease

[...]

Ricardo Cabezas¹, Marcos Fidel Avila¹, Janneth Gonzalez¹, Ramon dos Santos El-Bachá², Eliana Baez¹, Luis M. Garcia-Segura³, Juan Camilo Jurado Coronel¹, Francisco Capani⁴, Gloria Patricia Cardona-Gómez⁵, George E. Barreto¹ - Show less +6 more•Institutions (5)

Pontifical Xavierian University¹, Federal University of Bahia², Spanish National Research Council³, National Scientific and Technical Research Council⁴, University of Antioquia⁵

04 Aug 2014-Frontiers in Cellular Neuroscience

TL;DR: The implications of astrocyte functions in the protection of the blood–brain barrier, and in the development of Parkinson’s disease (PD) and related disorders are discussed.

...read moreread less

Abstract: TThe blood–brain barrier (BBB) is a tightly regulated interface in the Central Nervous System that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells, pericytes and astrocytes that create a neurovascular unit with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson´s Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the endothelial cells and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson´s disease and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

...read moreread less

312 citations

Cites background or methods from "GDNF, NGF and BDNF as therapeutic o..."

...…in different regions of the brain have shown mixed results, in part due to the mechanism of administration, and the growth factor inability to cross the BBB, therefore further research is needed in order to surpass this obstacle (Gill et al., 2003; Ramaswamy and Kordower, 2009; Allen et al., 2013)....
[...]
...Reduction in BDNF levels is associated with many pathological conditions such as PD, AD, Huntington Disease, ALS, depression and schizophrenia (Allen et al., 2013)....
[...]
...GDNF, secreted by astrocytes and pericytes, is essential for the survival of dopaminergic neurons, peripheral motor neurons and neurons from the locus coeruleus (Yasuda and Mochizuki, 2010; Allen et al., 2013)....
[...]
...…have been used including injections into the lumbar or ventricular CSF, viral vectors with growth factor genes, the temporal disruption of the BBB with hyperosmotic agent like mannitol, the use of linked peptides or peptidomimetic monoclonal antibodies or nanoparticles (Allen et al., 2013)....
[...]

Journal Article•DOI•

Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments

[...]

Panchanan Maiti, Jayeeta Manna¹, Gary L. Dunbar•Institutions (1)

University of Tennessee Health Science Center¹

25 Oct 2017-Translational neurodegeneration

TL;DR: A comprehensive overview of the current understanding of the molecular signaling pathways involved in Parkinson’s disease, particularly within the context of how genetic and environmental factors contribute to the initiation and progression of this disease is provided.

...read moreread less

Abstract: Gradual degeneration and loss of dopaminergic neurons in the substantia nigra, pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson’s disease (PD). In addition, half of the PD patients also exhibit frontostriatal-mediated executive dysfunction, including deficits in attention, short-term working memory, speed of mental processing, and impulsivity. The most commonly used treatments for PD are only partially or transiently effective and are available or applicable to a minority of patients. Because, these therapies neither restore the lost or degenerated dopaminergic neurons, nor prevent or delay the disease progression, the need for more effective therapeutics is critical. In this review, we provide a comprehensive overview of the current understanding of the molecular signaling pathways involved in PD, particularly within the context of how genetic and environmental factors contribute to the initiation and progression of this disease. The involvement of molecular chaperones, autophagy-lysosomal pathways, and proteasome systems in PD are also highlighted. In addition, emerging therapies, including pharmacological manipulations, surgical procedures, stem cell transplantation, gene therapy, as well as complementary, supportive and rehabilitation therapies to prevent or delay the progression of this complex disease are reviewed.

...read moreread less

309 citations

Cites background from "GDNF, NGF and BDNF as therapeutic o..."

...Recently, by manipulating several growth factors (such as FGF-2b, FGF8, SHH), researchers are able to generate DA-neurons from rodent embryonic stem cells (Fig....
[...]
...Similarly, the use of AAV2 to deliver gene for NGF, BDNF, GDNF, can increase regeneration of DA-neurons in SNpc and boost DA levels in striatum [198, 199]....
[...]
...One of the primary reasons for neuronal cell death in PD is the depletion of neuronal growth factors, such as decrease BDNF, NGF, GDNF, and FGF-2b [199, 209]....
[...]

Journal Article•DOI•

The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease.

[...]

Josiane Budni¹, Tatiani Bellettini-Santos¹, Francielle Mina¹, Michelle Lima Garcez¹, Alexandra I. Zugno¹ - Show less +1 more•Institutions (1)

Universidade do Extremo Sul Catarinense¹

01 Oct 2015-Aging and Disease

TL;DR: Considering that aging and AD are related to cognitive impairment, here it is discussed the involving of neurotrophic factors in the aging process and AD.

...read moreread less

Abstract: Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimer’s disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they overlap, as well as, the pathophysiological mechanism in each event. Considering that aging and AD are related to cognitive impairment, here we discuss the involving these neurotrophic factors in the aging process and AD.

...read moreread less

306 citations

1
2
3
4
…
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

Neuropathological stageing of Alzheimer-related changes.

[...]

Heiko Braak, Eva Braak

01 Jan 1991-Acta Neuropathologica

TL;DR: The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations, permitting the differentiation of six stages.

...read moreread less

Abstract: Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.

...read moreread less

13,699 citations

Journal Article•DOI•

Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.

[...]

Ruthie E. Amir¹, Ignatia B. Van den Veyver¹, Mimi Wan², Charles Q. Tran¹, Uta Francke², Huda Y. Zoghbi¹ - Show less +2 more•Institutions (2)

Baylor College of Medicine¹, Stanford University²

01 Oct 1999-Nature Genetics

TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.

...read moreread less

Abstract: Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females, with an incidence of 1 in 10,000-15,000 (ref. 2). Patients with classic RTT appear to develop normally until 6-18 months of age, then gradually lose speech and purposeful hand use, and develop microcephaly, seizures, autism, ataxia, intermittent hyperventilation and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood. As RTT occurs almost exclusively in females, it has been proposed that RTT is caused by an X-linked dominant mutation with lethality in hemizygous males. Previous exclusion mapping studies using RTT families mapped the locus to Xq28 (refs 6,9,10,11). Using a systematic gene screening approach, we have identified mutations in the gene (MECP2 ) encoding X-linked methyl-CpG-binding protein 2 (MeCP2) as the cause of some cases of RTT. MeCP2 selectively binds CpG dinucleotides in the mammalian genome and mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A (refs 12,13). In 5 of 21 sporadic patients, we found 3 de novo missense mutations in the region encoding the highly conserved methyl-binding domain (MBD) as well as a de novo frameshift and a de novo nonsense mutation, both of which disrupt the transcription repression domain (TRD). In two affected half-sisters of a RTT family, we found segregation of an additional missense mutation not detected in their obligate carrier mother. This suggests that the mother is a germline mosaic for this mutation. Our study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.

...read moreread less

4,503 citations

"GDNF, NGF and BDNF as therapeutic o..." refers background in this paper

...In the MECP2 mutant mouse model, as with Rett patients, there is a breathing dysfunction and reduced BDNF expression and TrkB activation in the medulla and pons....
[...]
...MECP2 binds to a BDNF promoter and is able to regulate BDNF expression....
[...]
...Disease progression in the MECP2 mice increased or decreased as BDNF was conditionally deleted or overexpressed....
[...]
...Pharmacology & Therapeutics xxx (2013) xxx–xxx JPT-06525; No of Pages 21 Contents lists available at SciVerse ScienceDirect Pharmacology & Therapeutics j ourna l homepage: www.e lsev ie r .com/ locate /pharmthera Associate editor: C. Stevenson GDNF, NGF and BDNF as therapeutic options for neurodegeneration Shelley J. Allen a,⁎, Judy J. Watson a, Deborah K. Shoemark a, Neil U. Barua b, Nikunj K. Patel b a Dorothy Hodgkin Building, Whitson St, Bristol BS1 3NY, UK b Dept of Neurosurgery Frenchay Hospital, Bristol BS16 1LE, UK Abbreviations: AAV2, adeno-associated viral vector; A APP intracellular domain; apoE, apolipoprotein E; AP Convection-enhanced delivery; CEI, (acetyl) cholinestera peptidase E; CSF, cerebrospinal fluid; DBS, Deep brain st binding protein 1; GFAP, glial fibrillary acidic protein; G internal; GSK3β, glycogen synthase kinase 3; GPI, gly Huntington's disease; HVA, homovanillic acid; 6-OHDA, ation; MECP2, methyl-CpG binding protein 2; MM tetrahydropyridine; NCAM, neural cell adhesion molecu anti inflammatory drugs; NT3, neurotrophin 3; NT4, neu emission tomography; PI3K, phosphoinositide 3-kinase nigra; SOD, superoxide dismutase; TBI, traumatic brain ceptor associated factor; TrkA receptor, Trypomysin rec Unified Parkinson's Disease Rating Scale; Vps10p, vacuo ⁎ Corresponding author at: Dorothy Hodgkin Building E-mail address: Shelley.allen@bristol.ac.uk (S.J. Allen 0163-7258/$ – see front matter © 2013 Elsevier Inc....
[...]
...This disorder is caused by mutations in the methyl-CpG binding protein 2 gene, MECP2 (Amir et al., 1999)....
[...]

Journal Article•DOI•

Neurotrophins: roles in neuronal development and function.

[...]

Eric J. Huang¹, Louis F. Reichardt¹•Institutions (1)

University of California, San Francisco¹

01 Jan 2001-Annual Review of Neuroscience

TL;DR: Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems, and control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.

...read moreread less

Abstract: Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems. Neurotrophins activate two different classes of receptors, the Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor superfamily. Through these, neurotrophins activate many signaling pathways, including those mediated by ras and members of the cdc-42/ras/rho G protein families, and the MAP kinase, PI-3 kinase, and Jun kinase cascades. During development, limiting amounts of neurotrophins function as survival factors to ensure a match between the number of surviving neurons and the requirement for appropriate target innervation. They also regulate cell fate decisions, axon growth, dendrite pruning, the patterning of innervation and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ion channels. These proteins also regulate many aspects of neural function. In the mature nervous system, they control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.

...read moreread less

3,968 citations

"GDNF, NGF and BDNF as therapeutic o..." refers background in this paper

...3 for more detail of the receptors) (Smeyne et al., 1994; Huang & Reichardt, 2001)....
[...]
...Thus, mice with homozygous knockout of NGF have severe sympathetic and sensory deficits and are not viable for more than a few weeks after birth (Crowley et al., 1994; Huang & Reichardt, 2001)....
[...]

Journal Article•DOI•

Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation.

[...]

Mark E. Gurney¹, Haifeng Pu¹, Arlene Y. Chiu², Mauro C. Dal Canto¹, Cynthia Y. Polchow¹, Denise D. Alexander¹, Jan Caliendo¹, Afif Hentati¹, Young W. Kwon¹, Han Xiang Deng¹, W. Chen¹, Ping Zhai¹, Robert L. Sufit¹, Teepu Siddique¹ - Show less +10 more•Institutions (2)

Northwestern University¹, City of Hope National Medical Center²

17 Jun 1994-Science

TL;DR: In this article, the authors found that mutations of human Cu,Zn superoxide dismutase (SOD) contribute to the pathogenesis of familial amyotrophic lateral sclerosis (ALS).

...read moreread less

Abstract: Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93--a change that has little effect on enzyme activity--caused motor neuron disease in transgenic mice. The mice became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS.

...read moreread less

3,958 citations

Journal Article•DOI•

The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function

[...]

Michael F. Egan, Masami Kojima¹, Masami Kojima², Joseph H. Callicott, Terry E. Goldberg, Bhaskar Kolachana, Alessandro Bertolino, Eugene Zaitsev², Bert Gold, David Goldman², Michael Dean, Bai Lu², Daniel R. Weinberger - Show less +9 more•Institutions (2)

National Institute of Advanced Industrial Science and Technology¹, National Institutes of Health²

24 Jan 2003-Cell

TL;DR: A role is demonstrated for BDNF and its val/met polymorphism in human memory and hippocampal function and it is suggested val/ met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF.

...read moreread less

3,599 citations