Reduced Fractalkine Levels Lead to Striatal Synaptic Plasticity Deficits in Huntington’s Disease

Kim, Anya; García-García, Esther; Straccia, Marco; Comella-Bolla, Andrea; Miguez, Andrés; Masana, Mercè; Alberch, Jordi; Canals, Josep M.; Rodrı́guez, Manuel J.

doi:10.3389/fncel.2020.00163

Cited by 37 publications

(39 citation statements)

References 94 publications

(111 reference statements)

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“…Reactive microglia and its involvement in HD pathology were extensively studied mainly in HD mouse models. Although amoeboid-shaped microglia were not detected in the striatum of R6/1 mice, PSD-95-positive puncta inside microglial cells indicate synaptic pruning that precedes symptom manifestation [ 147 ]. Moreover, the interaction between neurons and microglia that prevents the latter from becoming reactive, is affected in these mice [ 148 ].…”

Section: Molecular and Cellular Effects Of Oxidative Stress In Polyq Diseasesmentioning

confidence: 99%

Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases

et al. 2021

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Neurodegenerative polyglutamine (polyQ) disorders are caused by trinucleotide repeat expansions within the coding region of disease-causing genes. PolyQ-expanded proteins undergo conformational changes leading to the formation of protein inclusions which are associated with selective neuronal degeneration. Several lines of evidence indicate that these mutant proteins are associated with oxidative stress, proteasome impairment and microglia activation. These events may correlate with the induction of inflammation in the nervous system and disease progression. Here, we review the effect of polyQ-induced oxidative stress in cellular and animal models of polyQ diseases. Furthermore, we discuss the interplay between oxidative stress, neurodegeneration and neuroinflammation using as an example the well-known neuroinflammatory disease, Multiple Sclerosis. Finally, we review some of the pharmaceutical interventions which may delay the onset and progression of polyQ disorders by targeting disease-associated mechanisms.

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Section: Molecular and Cellular Effects Of Oxidative Stress In Polyq Diseasesmentioning

confidence: 99%

Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases

et al. 2021

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“…CX3CL1 expression is also inconsistent in other NDs. CX3CL1 levels in CSF of PD patients did not change compared to age-matched controls [132], whereas CX3CL1 levels in the putamen of HD patients were downregulated [133]. CX3CL1 mRNA levels in spinal cords of ALS model mice were reported to increase at 40 days of age but decrease at 90 and 120 days compared to those in WT mice [134].…”

Section: Cx3cl1mentioning

confidence: 89%

Physical Exercise-Induced Myokines in Neurodegenerative Diseases

Lee

Shin

Park

et al. 2021

IJMS

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Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), are disorders characterized by progressive degeneration of the nervous system. Currently, there is no disease-modifying treatments for most NDs. Meanwhile, numerous studies conducted on human and animal models over the past decades have showed that exercises had beneficial effects on NDs. Inter-tissue communication by myokine, a peptide produced and secreted by skeletal muscles during exercise, is thought to be an important underlying mechanism for the advantages. Here, we reviewed studies about the effects of myokines regulated by exercise on NDs and their mechanisms. Myokines could exert beneficial effects on NDs through a variety of regulatory mechanisms, including cell survival, neurogenesis, neuroinflammation, proteostasis, oxidative stress, and protein modification. Studies on exercise-induced myokines are expected to provide a novel strategy for treating NDs, for which there are no adequate treatments nowadays. To date, only a few myokines have been investigated for their effects on NDs and studies on mechanisms involved in them are in their infancy. Therefore, future studies are needed to discover more myokines and test their effects on NDs.

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“…Regarding microglia, we detected a mild recovery in both Iba1-immunoreactivity and microglia density in R6/1-shRTP801 mice (Figure 4 e-g). We also checked for morphological changes in microglia associated with an inflammatory response, but no genotype or shRNA effects were observed (Supplementary Figure 2), as previously described in the striatum of R6/1 mouse at this age [50]. Silencing hippocampal RTP801 neuronal levels in R6/1 mouse partially prevents neuroinflammatory events.…”

Section: Silencing Rtp801 Levels In R6/1 Mouse Hippocampal Neurons Prevents Neuroinflammatory Processesmentioning

confidence: 94%

RTP801/REDD1 is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease

Pérez‐Sisqués¹,

Solana‐Balaguer²,

Campoy‐Campos³

et al. 2021

Preprint

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RTP801/REDD1 is a stress-regulated protein whose levels are increased in several neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s diseases (HD). RTP801 downregulation ameliorates behavioral abnormalities in several mouse models of these disorders. In HD, RTP801 mediates mutant huntingtin (mhtt) toxicity in in vitro models and its levels are increased in human iPSCs, human postmortem putamen samples and in striatal synaptosomes from mouse models of the disease. Here, we investigated the role of RTP801 in the hippocampal pathophysiology of HD. We found that RTP801 levels are increased in the hippocampus of HD patients in correlation with gliosis markers. Although RTP801 expression is not altered in the hippocampus of the R6/1 mouse model of HD, neuronal RTP801 silencing in the dorsal hippocampus with shRNA-containing AAV particles ameliorates cognitive alterations. This recovery is associated with a partial rescue of synaptic markers and with a reduction of inflammatory events, especially microgliosis. Altogether, our results indicate that RTP801 could be a marker of hippocampal neuroinflammation in HD patients and a promising therapeutic target of the disease.

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Reduced Fractalkine Levels Lead to Striatal Synaptic Plasticity Deficits in Huntington’s Disease

Cited by 37 publications

References 94 publications

Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases

Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases

Physical Exercise-Induced Myokines in Neurodegenerative Diseases

RTP801/REDD1 is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington’s Disease

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