INT97861

Context Info Confidence 0.13 First Reported 2001 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 3 Total Number 3 Disease Relevance 1.11 Pain Relevance 0.09

peptidase activity (CTSA) mitochondrion (CTSA) small molecule metabolic process (CTSA) endoplasmic reticulum (CTSA) nucleolus (CTSA) nucleus (CTSA)

Anatomy Link Frequency B lymphocytes 2 CTSA (Homo sapiens)

Pain Link Frequency Relevance Heat anesthesia 1 89.04 imagery 3 49.96 peripheral neuropathy 6 5.00 Pain 3 5.00 Central nervous system 1 5.00 Paresthesia 1 5.00 depression 1 5.00 abdominal pain 1 5.00 Bioavailability 1 5.00 antidepressant 1 5.00

Disease Link Frequency Relevance Heat Disease 41 99.40 Death 6 85.68 Pick Disease Of The Brain 3 75.00 Gangliosidoses 1 74.80 Congenital Anomalies 2 72.04 Neurologic Manifestations 17 62.12 Virus Diseases 1 59.52 Acquired Immune Deficiency Syndrome Or Hiv Infection 2 57.68 Gauchers Disease 40 55.72 Paralysis 2 53.12

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Several animal studies also showed that depletion of GSL could be lethal or lead to neurological disturbance, and substrate reduction therapy should be aimed to reduce biosynthesis of GSL to a degree that can be tolerated by cells (Radin 1996).

Negative_regulation (reduce) of Gene_expression (biosynthesis) of GSL

1) Confidence 0.13 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2504062 Disease Relevance 0.31 Pain Relevance 0

These results are consistent with our hypothesis and with GSLs being centrally involved in the pathogenesis of NPC disease, and they suggest that drugs inhibiting GSL synthesis could have a similar ameliorating effect on the human disorder.

Negative_regulation (inhibiting) of Gene_expression (synthesis) of GSL associated with disease

2) Confidence 0.06 Published 2001 Journal Curr. Biol. Section Abstract Doc Link 11525744 Disease Relevance 0.50 Pain Relevance 0.09

The inhibition of GSL synthesis by miglustat has been demonstrated to reduce pathological intracellular lipid storage, improve fluid-phase endosomal uptake and normalize lipid transport in peripheral blood B lymphocytes of NP-C patients.44 This leads to a reduction of the potentially neurotoxic accumulation of gangliosides GM2 and GM3, lactosylceramide and glucosylceramide, and may prevent further neuronal damage.

Negative_regulation (inhibition) of Gene_expression (synthesis) of GSL in B lymphocytes

3) Confidence 0.03 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2781062 Disease Relevance 0.30 Pain Relevance 0

General Comments

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