Entity types

Below I have listed the different categories under which each entity operated on by the web crawler will fall.

1. Genes
2. Proteins
3. Molecules (drugs)
4. Transmitters (neurotransmitters, inflammatory cytokines etc.)
5. Receptors
6. Processes (e.g. apoptosis, glycolysis, oxidative phosphorylation)
7. Effect (upregulates, downregulates)
8. ALS type (SOD1 mouse, healthy yeast, limb-onset SALS…)
9. Laboratory anomalies (homocysteine ceruloplasmin, lipopolysaccharide)

From this initial data, the target is to distill something that can be used to

1. estimate the relevance of a given molecule as part of an ALS therapeutic cocktail as widely as possible
2. find pathways through which ALS could be subdivided into categories in order to enable separate therapeutics development for each category

 

Examples of entities in different categories

Proteins.

ceruloplasmin		Appears to be low in PALS’ serum.  Also present as an antioxidant in CNS.
SOD1	superoxide dismutase 1	One of the clumping proteins in ALS. Possible inter-cellular spreading agent.
TDP-43	tar DNA-binding protein 43	Major clumping protein in SALS.
FUS	fused in sarcoma	Another clumping protein.
MMP-9	matrix metalloproteinase 9	Seems to correlate with cell’s vulnerability in ALS.

 

Processes.

Astrocytosis		Occurs in ALS patients and presumably contributes to neuron destruction.
Endocytosis		Probable route through which SOD1 enters neurons.
Glycolysis		Possibly upregulated in ALS
Oxidative phosphorylation		Possibly downregulated in ALS.
Mitochondriopathy		One characteristic process in ALS
Protein folding		Place where something seems to go wrong.
Protein misfolding		Characteristic phenomenon in ALS.
Protein aggregation	Protein clumping	Characteristic phenomenon in ALS.
Axonal transport		Another place where things seem to go awry.
Apoptosis		Assumed mechanism of neuron destruction.
Neuroinflammation		Another potentiall mechanism for neuron destruction.
UPR activation		Presumed to occur
Stress granule formation		Takes place in affected neurons
ADAR2 downregulation		Present at least in some ALS forms
Protein recycling failures		Typically present in affected neurones
Dysregulation of cytosolic calcium		Typically present in affected neurones
ER stress	Endoplasmic reticulum stress	Typically present in affected neurones
Oxidative stress		One of the most prominent ALS processes
Hepatic steatosis		Apparently present in majority of PALS.
BBB leakage	leaking blood brain barrier	Occurs early on in disease progression.

 

Transmitters.

Glutamate		Assumed source of neurotoxicity
GABA		Counters the glutamate-induced excitation.
Nerve growth factors	NGF	Assumed to be deficient
C5a	Complement 5a	The “usual suspect” as regards the autoimmunity aspect.
HIF-1a	hypoxia induced factor 1 alpha

 

Molecules.

ALCAR	Acetyl-L-carnitine	Potentially helpful for cell metabolism
Riluzole		Counters glutamate toxicity
Baicalin	Chinese skullcap	Neuroprotective agent
Turmeric		Neuroprotective agent
Niacin
Niacinamide	Nicotinamide
Niacinamide riboside	Nicotinamide riboside

 

Laboratory anomalies.

Uric acid Elevated in some ALS forms

Creatine kinase

Free copper Possibly elevated

Homocysteine Elevated in some ALS forms

Neurofilaments  Found in both blood and CSF of PALS.