Mouse models of ALS: Past, present and future

@article{Lutz2018MouseMO,
  title={Mouse models of ALS: Past, present and future},
  author={Cathleen Lutz},
  journal={Brain Research},
  year={2018},
  volume={1693},
  pages={1-10}
}
  • C. Lutz
  • Published 1 August 2018
  • Biology, Medicine
  • Brain Research
Genome sequencing of both sporadic and familial patients of Amyotrophic Lateral Sclerosis (ALS) has led to the identification of new genes that are both contributing and causative in the disease. This gene discovery has come at an unprecedented rate, and much of it in recent years. Knowledge of these genetic mutations provides us with opportunities to uncover new and related mechanisms, increasing our understanding of the disease and bringing us closer to defined therapies for patients. Mouse… Expand
View on Elsevier
doi.org
58 Citations
Highly Influential Citations
2
Background Citations
18
Methods Citations
3

58 Citations

Citation Type

Citation Type

Nearly 30 Years of Animal Models to Study Amyotrophic Lateral Sclerosis: A Historical Overview and Future Perspectives
Amyotrophic lateral sclerosis (ALS) is a fatal, multigenic, multifactorial, and non-cell autonomous neurodegenerative disease characterized by upper and lower motor neuron loss. Several genetic… Expand
Exploring the alternative: Fish, flies and worms as preclinical models for ALS
TLDR
It is concluded that small animal models will not replace rodent models, yet they clearly represent an important asset for preclinical studies. Expand
SOD1-targeting therapies for neurodegenerative diseases: a review of current findings and future potential
TLDR
A literature search of publications pertaining to SOD1-ALS and its treatment from 1992-present using the MEDLINE database form the basis for this review. Expand
Animal models of amyotrophic lateral sclerosis: a comparison of model validity
TLDR
The zebrafish model of environmentally-induced motor neuron degeneration displays convincing features of face validity with many hallmarks of ALS-like features, and weakness in construct validity; however, the value of this model may lie in its potential to be more representative of the pathogenic features underlying sporadic ALS cases. Expand
Cell-based Research and Therapy for Amyotrophic Lateral Sclerosis: Promises and Challenges
TLDR
Cell therapy is emerging as a promising therapeutic alternative for ALS and the advent of induced pluripotent stem cells (iPSCs) has enabled the development of patient-specific cell lines, a valuable tool to investigate in vitro molecular mechanisms of the disease and therapies in different genetic backgrounds. Expand
Harnessing the Potential of Human Pluripotent Stem Cell-Derived Motor Neurons for Drug Discovery in Amyotrophic Lateral Sclerosis: From the Clinic to the Laboratory and Back to the Patient
Amyotrophic Lateral Sclerosis (ALS) is a motor neurodegenerative disorder whose cellular hallmarks are the progressive death of motor neurons (MNs) located in the anterior horn of the spinal cord,… Expand
Modeling ALS using iPSCs: Is it possible to reproduce the phenotypic variations observed in patients in vitro?
TLDR
The pathophysiological markers detected in cells differentiated from iPSCs of ALS patients are summarized and could be useful for drug screening, through stratifying patients according to their genetic background. Expand
Locus-specific analysis of Transposable Elements during the progression of ALS in the SOD1G93A mouse model
TLDR
It is shown that TEs become up-regulated at the early stages of the disease, and via statistical associations, it is speculated that they can regulate several genes, which in turn might be contributing to the genetic dysfunction observed in ALS. Expand
P2X7 Receptor Antagonism as a Potential Therapy in Amyotrophic Lateral Sclerosis
This review focuses on the purinergic ionotropic receptor P2X7 (P2X7R) as a potential target for developing drugs that delay the onset and/or disease progression in patients with amyotrophic lateral… Expand
TDP-43: A Key Therapeutic Target beyond Amyotrophic Lateral Sclerosis.
TLDR
The recent studies of TDP-43, its relation to neurodegenerative diseases, and the therapeutic strategies for restoring its homeostasis with small molecules are summarized. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 130 REFERENCES
Novel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications
TLDR
The identification of these seven novel genes has been important in unravelling the molecular mechanisms underlying ALS, and therapeutics targeting these pathways could be useful for a broad group of patients stratified by genotype. Expand
From animal models to human disease: a genetic approach for personalized medicine in ALS
TLDR
Subgroups of specific ALS-linked gene mutations are used to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Expand
Pathogenesis of FUS-associated ALS and FTD: insights from rodent models
TLDR
The evidence for FUS pathogenicity in ALS/FTD is discussed, the experimental approaches used and phenotypic features of FUS rodent models reported to date are reviewed, and their contribution to the understanding of pathogenic mechanisms are outlined. Expand
Design, power, and interpretation of studies in the standard murine model of ALS
  • Sean Scott, J. E. Kranz, +9 authors J. Heywood
  • Medicine
  • Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases
  • 2008
TLDR
The majority of published effects are most likely measurements of noise in the distribution of survival means as opposed to actual drug effect, so a minimum study design is recommended for this mouse model to best address and manage this inherent noise. Expand
Gene discovery in amyotrophic lateral sclerosis: implications for clinical management
TLDR
It is observed that many gene variants associated with ALS have effect sizes between those of mutations that greatly increase risk and those of common variants that have a small effect on risk, and this observation is combined with insights from next-generation sequencing to explore the implications for genetic counselling. Expand
Progress in Therapy Development for Amyotrophic Lateral Sclerosis
TLDR
Current trends in experimental therapeutics for ALS are explored with emphasis on the emerging interest in axon guidance signaling pathways as novel targets for pharmacological support of neural cytoskeletal structure and function in order to slow ALS. Expand
NEK1 mutations in familial amyotrophic lateral sclerosis.
TLDR
The association between NEK1 variants and familial ALS was assessed using whole exome sequence data of 265 familial ALS index patients and 827 control individuals to assess the variant burden inNEK1. Expand
C57BL/6J congenic Prp-TDP43A315T mice develop progressive neurodegeneration in the myenteric plexus of the colon without exhibiting key features of ALS
TLDR
The disease phenotype was gender- and genetic background-dependent, with congenic C57BL/6J male mice exhibiting the most aggressive form of the disease, with neither gender exhibited compelling ALS-like neuromuscular deficits, irrespective of age. Expand
A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity
TLDR
These unique mice allow us to further the understanding of ALS by separating the central motor neuron body degeneration and the peripheral effects from a fALS mutation expressed at endogenous levels. Expand
NEK1 variants confer susceptibility to amyotrophic lateral sclerosis
TLDR
In a new screening strategy, gene-burden analyses trained with established ALS genes are performed and a significant association between loss-of-function (LOF) NEK1 variants and FALS risk is identified. Expand
...
1
2
3
4
5
...