Neurotrophic growth factors for the treatment of amyotrophic lateral sclerosis: where do we stand ?

Henriques, Alexandre Cruz; Pitzer, Claudia; Schneider, Armin

doi:10.3389/fnins.2010.00032

Cited by 69 publications

(65 citation statements)

References 204 publications

(235 reference statements)

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“…Defects in the retrograde transport of neurotrophic factors has been proposed to contribute to the neuronal death characteristic of ALS (Henriques et al, 2010). Processive motility of signaling endosomes in neurons from SOD1 G93A mice was shown to be disrupted by frequent pauses and switches (Perlson et al, 2009); in vivo analysis of transport in this model also shows enhanced pausing of cargos along the axon (Bilsland et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein

Klinman

Holzbaur

2015

Cell Reports

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Summary Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin dependent kinase 5 (CDK5) activity, driven by the stress-induced activator p25, is also observed in these diseases. Here, we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of Amyotrophic Lateral Sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration.

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Section: Resultsmentioning

confidence: 99%

Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein

Klinman

Holzbaur

2015

Cell Reports

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“…Since the properties of NTFs give them therapeutic potential for neurological disorders, they have been extensively studied in the field of experimental neurology, and applied in animal models of neurodegeneration, e.g. Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease (AD) (Airavaara et al, 2012; Henriques et al, 2010; Schulte-Herbruggen et al, 2008). In these models, both GDNF and BDNF, as well as several other NTFs, protect neurons from toxins and injury.…”

Section: Bdnf Gdnf and Dopaminementioning

confidence: 99%

Update of neurotrophic factors in neurobiology of addiction and future directions

Koskela

Bäck

Võikar

et al. 2017

Neurobiology of Disease

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Drug addiction is a chronic brain disease and drugs of abuse cause long lasting neuroadaptations. Addiction is characterized by the loss of control over drug use despite harmful consequences, and high rates of relapse even after long periods of abstinence. Neurotrophic factors (NTFs) are well known for their actions on neuronal survival in the peripheral nervous system. Moreover, NTFs have been shown to be involved in synaptic plasticity in the brain. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are two of the most studied NTFs and both of them have been reported to increase craving when administered into the mesocorticolimbic dopaminergic system after drug self-administration. Here we review recent data on BDNF and GDNF functions in addiction-related behavior and discuss them in relation to previous findings. Finally, we give an insight into how new technologies could aid in further elucidating the role of these factors in drug addiction.

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“…In developing motor neurons, brain-derived neurotrophic factor (BDNF) and neurotrophins (NT) 3 and 4 mediate cell survival through their cognate Trk receptors, TrkB or C (Kaplan and Miller, 2000). Similarly, after nerve lesion and in animal models of motor neuron disease, BDNF and NT3 can protect and repair motor neurons (Yuen and Mobley, 1995;Wiese et al, 2004;Henriques et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment

Matusica

Alfonsi

Turner

et al. 2015

Journal of Cell Science

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The p75 neurotrophin receptor ( p75 NTR ; also known as NGFR) can mediate neuronal apoptosis in disease or following trauma, and facilitate survival through interactions with Trk receptors. Here we tested the ability of a p75NTR -derived trophic cell-permeable peptide, c29, to inhibit p75 NTR -mediated motor neuron death. Acute c29 application to axotomized motor neuron axons decreased cell death, and systemic c29 treatment of SOD1 G93A mice, a common model of amyotrophic lateral sclerosis, resulted in increased spinal motor neuron survival mid-disease as well as delayed disease onset. Coincident with this, c29 treatment of these mice reduced the production of p75 NTR cleavage products. Although c29 treatment inhibited mature-and pro-nerve-growth-factor-induced death of cultured motor neurons, and these ligands induced the cleavage of p75 NTR in motor-neuron-like NSC-34 cells, there was no direct effect of c29 on p75 NTR cleavage. Rather, c29 promoted motor neuron survival in vitro by enhancing the activation of TrkB-dependent signaling pathways, provided that low levels of brain-derived neurotrophic factor (BDNF) were present, an effect that was replicated in vivo in SOD1 G93A mice. We conclude that the c29 peptide facilitates BDNF-dependent survival of motor neurons in vitro and in vivo.

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Neurotrophic growth factors for the treatment of amyotrophic lateral sclerosis: where do we stand ?

Cited by 69 publications

References 204 publications

Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein

Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein

Update of neurotrophic factors in neurobiology of addiction and future directions

Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment

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