TABLE 1.
Summary of altered proteins and mRNAs involved in local translation in different nervous system pathologies.
| Disease | Protein/mRNA | Altered mechanism on local translation | Model system | References |
| ALS/FTD | TDP-43 | Abnormal trafficking of futsch/Map1b mRNAs to neurites leading to cytoskeleton defects | Drosophila model of ALS in vivo, ALS vs. control postmortem brain tissue | Coyne et al., 2014 |
| FUS | Stress-mediated inhibition of intra-axonal translation | HEK-293 cell line and zebrafish embryo spinal cords; mutant FUS mice and mouse hippocampal neuron culture | Bosco et al., 2010; Lopez-Erauskin et al., 2018 | |
| C9orf72 | mRNP granules mislocalization to neuritic compartments affecting to branching | Rat spinal cord neuron culture, Drosophila model in vivo | Burguete et al., 2015 | |
| SMA | SMN | Actb, Nrn1, Gap43, Anxa2 mislocalization altering neurite growth, presynaptic function, and cytoskeleton Repression of axonal mTOR through miR-183 | NSC-34 cell line; mouse motor neuron culture Rat hippocampal, cortical, and motor neuron culture | Rage et al., 2013; Fallini et al., 2014, 2016; Kye et al., 2014; Rihan et al., 2017 |
| AD | Mapt | Mapt mislocalization to dendrites and hyperphosphorylation | Mouse hippocampal neuron culture, WT vs. Tau KO mice; hippocampal neuron culture from WT and Fyn KO mice, HEK-293 cell line, WT, APP23 and FynCA Tg mouse models in vivo | Kobayashi et al., 2017; Li and Gotz, 2017 |
| Atf4 | Atf4 recruitment to axons induced by Aβ oligomers, leading to neuronal death | Rat hippocampal neuron culture, mouse model in vivo, AD and control postmortem human brain tissue | Baleriola et al., 2014; Walker et al., 2018 | |
| PD | UPR genes | UPR altered. A compartment-dependent UPR involving local translation? | α-synuclein Tg mice | Hetz and Saxena, 2017 |
| LRRK2 | Deregulation of global eIF4E/4E-BP. Defects in axonal 4E-BP dependent translation? Axonal microRNAs deregulation? | HEK-293 and SH-SY5Y cell lines; rat superior cervical ganglia neuron culture; rat cortical neuron culture, WTvs. LRRK2 KO mice | Imai et al., 2008; Kumar et al., 2010; Natera-Naranjo et al., 2010; Herzig et al., 2011; Trancikova et al., 2012 | |
| PINK1/PARK2 | Pumilio and Glorund/hnRNP-F displacement: altered translation in the mitochondrion surface (within axons?) due to PINK1/PARK2 mutations. | Drosophila PINK1 model and HEK 293T cell line | Mouton-Liger et al., 2017; Martinez et al., 2019 | |
| HD | HTT | Impaired dendritic levels of Actb mRNA, Ago2 protein and P-bodies Altered axonal BDNF delivery leading to neurotoxicity | Homozygous Htt mutant cell lines (109Q/109Q); HeLa S3 cells Flagged-Htt590; rat cortical neuron culture and brain sections | Gauthier et al., 2004; Savas et al., 2008; Ma et al., 2010, 2011; Savas et al., 2010 |
| ASD and FXS | FMRP | Deregulation of local mRNAs linked to abnormal spine morphology and plasticity Upregulation of dendritic Dlg4 translation through inhibition of miR-125a with spine morphology defects Dendritic mTOR upregulation | Rat hippocampal neuron culture; cortical neuron culture from Fmr1 KO mice; in vivo Fmr1 KO mouse model; Organotypic hippocampal slice cultures from Fmr1 KO mice | Antar et al., 2004; Muddashetty et al., 2011; Pyronneau et al., 2017; Banerjee et al., 2018; Feuge et al., 2019 |
| DS | Dscam | Upregulation of dendritic mRNA and protein levels with defects in dendrite branching | Mouse hippocampal neuron culture from Ts1Cje mice, DS mouse model | Alves-Sampaio et al., 2010 |
| Bdnf | Upregulation within dendrites leading to an aberrant activation of dendritic translation | In vitro hippocampal dendrites from Ts1Cje mice | Troca-Marin et al., 2011; Swanger and Bassell, 2013 | |
| Other | Bdnf (depression and bipolar disorder) | Dendritic Bdnf localization to dendrites disrupted | Ts1 Cje mouse hippocampal neuron culture | Swanger and Bassell, 2013 |
| Pumilio-2 (epilepsy) | Erroneous mRNAs localization to axons Upregulation of overall translation in axons with branching defects | In vivo 5 month Pum2 gene-trap mice; Pum2 knockdown in primary dorsal root ganglion rat neuron culture and mouse model in vivo | Follwaczny et al., 2017; Martinez et al., 2019 |
ALS, amyotrophic lateral sclerosis; FTD, frontotemporal dementia; SMA, spinal muscular atrophy; AD, Alzheimer’s disease; PD, Parkinson’s disease; HD, Huntington’s disease; ASD, autism spectrum disorders; FXS, fragile-X syndrome; DS: down syndrome.