INT313435

Context Info Confidence 0.43 First Reported 2010 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 9 Disease Relevance 1.60 Pain Relevance 0.64

cytosol (Th) mitochondrion (Th) transport (Syp) oxidoreductase activity (Th) nucleus (Th) protein complex (Syp)

Anatomy Link Frequency brain 2 neuronal 1 olfactory bulbs 1 Syp (Mus musculus) Th (Mus musculus)

Pain Link Frequency Relevance Heat Dopamine 180 97.36 Substantia nigra 81 84.96 Catecholamine 54 7.60 midbrain 36 5.00 adenocard 9 5.00 Neurotransmitter 9 5.00 Tetrahydrobiopterin 9 5.00 Pain 9 5.00 lidocaine 9 5.00 Potency 9 5.00

Disease Link Frequency Relevance Heat Aging 27 94.40 Parkinson's Disease 162 93.52 Targeted Disruption 90 92.40 Apoptosis 27 88.00 Toxicity 18 84.64 Stress 18 26.64 Pain 9 5.00 Disease 9 5.00 Injury 9 5.00 Neurodegenerative Disease 9 5.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

To determine whether a-Syn affects TH in other dopaminergic tissues, we evaluated olfactory bulbs from the same 30 mice described above.

Syn Regulation (affects) of TH in olfactory bulbs

1) Confidence 0.43 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.08 Pain Relevance 0.07

These data provide the first evidence that both WT a-Syn and A53T mutant a-Syn regulate TH and PP2A similarly in vitro and in vivo.

Syn Regulation (regulate) of TH

2) Confidence 0.43 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.03

These data provide the first evidence that both WT a-Syn and A53T mutant a-Syn regulate TH and PP2A similarly in vitro and in vivo.

Syn Regulation (regulate) of TH

3) Confidence 0.43 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.03

a-Syn overexpression in WT-Syn++ and A53T-Syn++ mice reduced TH-Ser-19 phosphorylation in vivo, suggesting that, as in dopaminergic cell lines, both forms of a-Syn regulate TH similarly in the brain.

Syn Regulation (regulate) of TH in brain

4) Confidence 0.32 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.38 Pain Relevance 0.13

Collectively our findings provide compelling support for physiological regulation of PP2A and TH by a-Syn, with a-Syn Ser-129 phosphorylation attenuating the effects.

Syn Regulation (regulation) of TH

5) Confidence 0.19 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.32 Pain Relevance 0

Our early in vitro findings identified an inhibitory role for a-Syn on TH (9) occurring by the effects on TH- Ser-40 (43).

Syn Regulation (role) of TH

6) Confidence 0.19 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.22 Pain Relevance 0.13

These findings parallel our data from MN9D cells (Fig. 1) and mouse striatum (Fig. 3A), identifying a previously undescribed effect of a-Syn on TH in nigral neuronal cell bodies in vivo.

Syn Regulation (effect) of TH in neuronal

7) Confidence 0.19 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.07 Pain Relevance 0.08

Because a-Syn Ser-129 phosphorylation reduced the a-Syn effect on TH and PP2A, a shift in a-Syn levels along with changes in the levels of Ser(P)-129 could dysregulate a-Syn-modulated proteins, especially in aging brain (62).

Syn Regulation (effect) of TH in brain associated with aging

8) Confidence 0.19 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.30 Pain Relevance 0.03

Those studies provided the basis for the present work in which we evaluated a-Syn effects on TH-Ser(P)-19 in vitro.

Syn Regulation (effects) of TH-Ser

9) Confidence 0.17 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.24 Pain Relevance 0.12

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