I would like to do some research about ALS, mSOD is not a good model, does anyone have some suggestions which model would be good or which novel model of ALS (in vitro and mouse too) would be better than currently existed ones for therapeutic and diagnostic purpose?
I would like to study the mechanisms of cell death during ALS, also to test different compounds to use as potential drugs.
I think that the best model to study ALS is the NSC-34-SOD. This cell line is an hybrid of tumour and embrionary motoneuron spinal cord but the differentiation of cell line express a lot of properties of motoneurons. Another option is use an organotypic spinal cord with a compound to generate ROS.
I have been thinking about a good model for Alzheimer's based on my own research on the Na-pump controlling the ionic homeostasis and electromagnetic signals in area specific brain. I am currently writing an article on this for my RG site. However, the information is already in my site in a scattered manner. The new article will present them in a more organized way. Please go to my site to have some feeling.
Get in touch with Prof. Jochen Prehn at the Royal College Of Surgeons in Ireland, he is one of the experts and has both in vitro and in vivo models.
(i) SOD1(G93A) mice, low copy (Jackson labs strain B6.Cg-Tg(SOD1*G93A)dl1Gur/J ; these mice are widely used and develop slowly progressive ALS. The low expression of the transgene allows a much slower disease progression that is more relevant to human ALS.
(ii) TDP-43(Q331K) mice (Jackson labs strain B6N.Cg-Tg(Prnp-TARDBP*Q331K)103Dwc/J): these mice develop slowly progressive loss of motor neurons (19), but no gastro-intestinal dysfunction as developed by other TDP-43 mouse strains.
I look for also a model oe SLA for studied effects of somme compounds. This link explain many mouse model. I have found a Zebrafish model (Dr Ramesh Tennore) which seems very interressing for studied effect of compounds.
SOD models are very usefull for studied mechanisms but all molecules founds have not been validated in humans then.
I have quickly look the SOD1(G93A) e TDP-43 model, it's seems interessig but probably expensive how many model. If somebody-have information on this model and cost, thank you
http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=4&ved=0CEcQFjAD&url=http%3A%2F%2Fwww.researchals.org%2Fuploaded_files%2Fp4l_jax_sod1manual_20091202_29aPcx.pdf&ei=XcyBVNGbB4bwUomXgfgP&usg=AFQjCNGJMW8y8bfAglNTJV8k_oJWJnNFeA
http://www.ncbi.nlm.nih.gov/pubmed/24570655
Hi, I just published a paper in RG entitled "Neurodegeneration due to the defective regulation of the Na, K-ATPase system by its cytosolic NaAF (170 k Da) activator: A Hypothesis", and I believe you will be interested in it.
I have presented strong evidences in favor of the proposed hypothesis, and believe it will open up new investigations on Alzheimer's in order to having a better management and possible reversal with time.
There is no simple answer to this question. We are learning more and more that ALS is likely a heterogenous disorder with similar clinical manifestations characterized by upper and lower motor neuron dysfunction and degeneration ultimately leading to muscle atrophy and cell death. The best models to broadly study disease progression in a way that most closely models human ALS probably remain SOD1 mouse models. The initial pathogenic insult may not be in common with the majority of human hereditary ALS, but the mice exhibit key elements of human ALS, ie, lower motor neuron degeneration, muscle weakness, spasticity, protein aggregation, muscle atrophy, astrocytosis, microgliosis, etc.. There are clear limitations, however. First, there is little/no evidence of TDP43+ inclusion bodies as are seen in most human clinical cases. Unfortunately, to my knowledge, there are no very good whole animal models of other forms of hereditary ALS and sporadic ALS can't be easily modeled because the etiology is unclear. However, approaches that use primary neuronal cultures and aim to transfect with mutant genes that are associated with ALS risk have value. Even more, induced pluripotent stem cells from patients living with ALS can also have value. The weaknesses with these are that it is nearly impossible to generate a functional motor unit with motor neuron synapsing with myocyte and supported by microglia, astrocytes, oligodendroglia, etc...all of which seem to play important roles in ALS disease progression. Basically, I suggest that you "pick your poison" as far as disease models go. Understand the limitations of whichever models you choose to work with and be prepared to acknowledge the limitations and have plans to hedge your bets with multiple models to better triangulate on the "truth".
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