Neurotrophic/Growth factors
|
Insulin |
Saute et al., 2011Saute JA, da Silva AC, Muller AP, Hansel G, de Mello AS, Maeda F, Vedolin L, Saraiva-Pereira ML, Souza DO, Arpa J et al. (2011) Serum insulin-like system alterations in patients with spinocerebellar ataxia type 3. Mov Disord 26:731-735.
|
46 |
42 |
Serum |
Insulin levels: 6.2(3.5) uIU/mL* |
Insulin levels: 9.5(6) uIU/mL |
No |
No |
|
|
|
|
Serum |
HOMA2-%B: 83.9(35) |
HOMA2-%B: 92.9(50.5) |
No |
No |
|
|
|
|
Serum |
Log(HOMA2-%S): 4.8(0.55)** |
Log(HOMA2-%S): 4.35(0.63) |
No |
No |
IGF-1 |
Saute et al., 2011Saute JA, da Silva AC, Muller AP, Hansel G, de Mello AS, Maeda F, Vedolin L, Saraiva-Pereira ML, Souza DO, Arpa J et al. (2011) Serum insulin-like system alterations in patients with spinocerebellar ataxia type 3. Mov Disord 26:731-735.
|
46 |
42 |
Serum |
Total IGF-1: 114.5(32.2) ng/mL |
Total IGF-1: 117.4(36.3) ng/mL |
No |
No |
|
|
|
|
Serum |
Free IGF-1 (IGF-1/IGFBP-3 molar ratio): 0.36(0.24)* |
0.23(0.12) |
No |
No |
IGFBP-1 |
Saute et al., 2011Saute JA, da Silva AC, Muller AP, Hansel G, de Mello AS, Maeda F, Vedolin L, Saraiva-Pereira ML, Souza DO, Arpa J et al. (2011) Serum insulin-like system alterations in patients with spinocerebellar ataxia type 3. Mov Disord 26:731-735.
|
46 |
42 |
Serum |
2.67(1.8) ng/mL ** |
1.32(0.98) |
No |
No |
IGFBP-3 |
Saute et al., 2011Saute JA, da Silva AC, Muller AP, Hansel G, de Mello AS, Maeda F, Vedolin L, Saraiva-Pereira ML, Souza DO, Arpa J et al. (2011) Serum insulin-like system alterations in patients with spinocerebellar ataxia type 3. Mov Disord 26:731-735.
|
46 |
42 |
Serum |
1.4(0.8) ug/mL** |
2.01(0.36) |
No |
No |
Activation of pro-inflammatory factors
|
FCGR3B gene |
Raposo et al., 2015Raposo M, Bettencourt C, Maciel P, Gao F, Ramos A, Kazachkova N, Vasconcelos J, Kay T, Rodrigues AJ, Bettencourt B et al. (2015) Novel candidate blood-based transcriptional biomarkers of Machado-Joseph disease. Mov Disord 30:968-975.
|
12 (DC) 42 (CC) |
12 (DC) 35 (CC) |
RNA from peripheral blood |
FC: 2.597*; SD not informed |
NA |
ND |
Yes* FC and SD not informed |
TNFSF14 gene |
Raposo et al., 2015Raposo M, Bettencourt C, Maciel P, Gao F, Ramos A, Kazachkova N, Vasconcelos J, Kay T, Rodrigues AJ, Bettencourt B et al. (2015) Novel candidate blood-based transcriptional biomarkers of Machado-Joseph disease. Mov Disord 30:968-975.
|
12 (DC) 42 (CC) |
12 (DC) 35 (CC) |
RNA from peripheral blood |
FC: 1.687; SD not informed |
NA |
ND |
Yes (short disease duration only)* FC and SEM not informed |
SELPLG gene |
Raposo et al., 2015Raposo M, Bettencourt C, Maciel P, Gao F, Ramos A, Kazachkova N, Vasconcelos J, Kay T, Rodrigues AJ, Bettencourt B et al. (2015) Novel candidate blood-based transcriptional biomarkers of Machado-Joseph disease. Mov Disord 30:968-975.
|
12 (DC) 42 (CC) |
12 (DC) 35 (CC) |
RNA from peripheral blood |
FC: 1.324*; SD not informed |
NA |
ND |
No |
Activation of astrocytes
|
miR-34b |
Shi et al., 2014Shi Y, Huang F, Tang B, Li J, Wang J, Shen L, Xia K and Jiang H (2014) MicroRNA profiling in the serums of SCA3/MJD patients. Int J Neurosci 124:97-101.
|
9 (DC) 35 (VC) |
7 (DC) 25 (VC) |
Serum |
Up-regulated: Ratio Cases/Controls: 4.79*** SD not informed |
NA |
No |
No |
miR-29a |
Shi et al., 2014Shi Y, Huang F, Tang B, Li J, Wang J, Shen L, Xia K and Jiang H (2014) MicroRNA profiling in the serums of SCA3/MJD patients. Int J Neurosci 124:97-101.
|
9 (DC) 35 (VC) |
7 (DC) 25 (VC) |
Serum |
Down-regulated: Ratio Controls/Cases: 4.7* |
NA |
No |
No |
miR-25 |
Shi et al., 2014Shi Y, Huang F, Tang B, Li J, Wang J, Shen L, Xia K and Jiang H (2014) MicroRNA profiling in the serums of SCA3/MJD patients. Int J Neurosci 124:97-101.
|
9 (DC) 35 (VC) |
7 (DC) 25 (VC) |
Serum |
Down-regulated: Ratio Controls/Cases: 2.04* |
NA |
No |
Yes (longer disease duration only)* atio and SEM not informed |
miR-125b |
Shi et al., 2014Shi Y, Huang F, Tang B, Li J, Wang J, Shen L, Xia K and Jiang H (2014) MicroRNA profiling in the serums of SCA3/MJD patients. Int J Neurosci 124:97-101.
|
9 (DC) 35 (VC) |
7 (DC) 25 (VC) |
Serum |
Down-regulated: Ratio Controls/Cases: 2.1* |
NA |
No |
Yes (longer disease duration only)* Ratio and SEM not informed |
GFAP |
Shi et al., 2014Shi Y, Huang F, Tang B, Li J, Wang J, Shen L, Xia K and Jiang H (2014) MicroRNA profiling in the serums of SCA3/MJD patients. Int J Neurosci 124:97-101.
|
136 |
151 |
Serum |
8.86(4.33) ng/mL ** |
3.93 2.38 |
No |
No |
Eotaxin |
da Silva Carvalho et al.,2016da Silva Carvalho G, Saute JA, Haas CB, Torrez VR, Brochier AW, Souza GN, Furtado GV, Gheno T, Russo A, Monte TL et al. (2016) Cytokines in Machado Joseph Disease/Spinocerebellar Ataxia 3. Cerebellum 15:518-525.
Saute et al., 2014Saute JA, de Castilhos RM, Monte TL, Schumacher-Schuh AF, Donis KC, D’Ávila R, Souza GN, Russo AD, Furtado GV, Gheno TC et al. (2014) A randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease. Mov Disord 29:568-573.
|
66 (Symptomatic) 13 (Asymptomatic) |
43 |
Serum |
Symptomatic carriers logEotaxin: 1.3 (SE=0.1) (SD: 0.50724). Asymptomatic carriers logEotaxin: 2.3 (SE=0.2) *** |
Controls: 1.33 (SE=0.09) |
No |
No |
G-protein coupled receptors
|
P2RY13 gene |
Raposo et al., 2015Raposo M, Bettencourt C, Maciel P, Gao F, Ramos A, Kazachkova N, Vasconcelos J, Kay T, Rodrigues AJ, Bettencourt B et al. (2015) Novel candidate blood-based transcriptional biomarkers of Machado-Joseph disease. Mov Disord 30:968-975.
|
12 (DC) 42 (CC) |
12 (DC) 35 (CC) |
RNA from peripheral blood |
FC: 1.665*; SD not informed |
NA |
ND |
No |
Enzyme
|
|
|
|
|
|
|
|
|
CLC gene |
Raposo et al.,2015Raposo M, Bettencourt C, Maciel P, Gao F, Ramos A, Kazachkova N, Vasconcelos J, Kay T, Rodrigues AJ, Bettencourt B et al. (2015) Novel candidate blood-based transcriptional biomarkers of Machado-Joseph disease. Mov Disord 30:968-975.
|
12 (DC) 42 (CC) |
12 (DC) 35 (CC) |
RNA from peripheral blood |
FC: 2.041 SD not informed |
NA |
ND |
Yes* FC and SD were not informed |
Others
|
|
|
|
|
|
|
|
|
SLA gene |
Raposo et al., 2015Raposo M, Bettencourt C, Maciel P, Gao F, Ramos A, Kazachkova N, Vasconcelos J, Kay T, Rodrigues AJ, Bettencourt B et al. (2015) Novel candidate blood-based transcriptional biomarkers of Machado-Joseph disease. Mov Disord 30:968-975.
|
12 (DC) 42 (CC) |
12 (DC)35 (CC) |
RNA from peripheral blood |
FC: 1.333 SD not informed; |
NA |
ND |
Yes (short disease duration only)* FC and SD not informed |
Markers of neuronal/glial loss
|
NSE |
Tort et al., 2005Tort AB, Portela LV, Rockenbach IC, Monte TL, Pereira ML, Souza DO, Rieder CR and Jardim LB (2005) S100B and NSE serum concentrations in Machado Joseph disease. Clin Chim Acta 351:143-148.
|
22 |
22 |
Serum |
8.05(4.2) ng/mL *** |
4.65 (1.80) ng/mL |
EDSS (R=-0.729*) |
No |
|
Zhou et al., 2011Zhou J, Lei L, Shi Y, Wang J, Jiang H, Shen L and Tang B (2011) Serum concentrations of NSE and S100B in spinocerebellar ataxia type 3/Machado-Joseph disease. Zhong Nan Da Xue Xue Bao Yi Xue Ban 36:504-510.
|
102 |
100 |
Serum |
6.95(2.83) ng/mL*** |
4.83 (1.70) ng/mL |
ICARS R=0.242* SARA R=0.248* ICARS = 26.68 (13.37)SARA = 9.98 (4.65) |
R=0.259** |
S100B |
Tort et al., 2005Tort AB, Portela LV, Rockenbach IC, Monte TL, Pereira ML, Souza DO, Rieder CR and Jardim LB (2005) S100B and NSE serum concentrations in Machado Joseph disease. Clin Chim Acta 351:143-148.
|
22 |
22 |
Serum |
0.108(0.073) ug/l |
0.082 (0.042) ug/l |
No |
R=0.452* |
|
Zhou et al., 2011Zhou J, Lei L, Shi Y, Wang J, Jiang H, Shen L and Tang B (2011) Serum concentrations of NSE and S100B in spinocerebellar ataxia type 3/Machado-Joseph disease. Zhong Nan Da Xue Xue Bao Yi Xue Ban 36:504-510.
|
102 |
100 |
Serum |
0.07(0.06) ng/ml *** |
0.05 (0.02) ng/ml |
No |
No |
Neurofilament |
Wilke et al.,2018Wilke C, Bender F, Hayer SN, Brockmann K, Schöls L, Kuhle J and Synofzik M (2018) Serum neurofilament light is increased in multiple system atrophy of cerebellar type and in repeat-expansion spinocerebellar ataxias: a pilot study. J Neurol 265:1618-1624.
|
8 |
16 |
Serum |
70 pg/ml (range: 40 to 105) *** |
22 pg/ml (8 to 35) |
No |
No |
Oxidative Stress Markers
|
DCFH-DA |
de Assis et al., 2017de Assis AM, Saute JAM, Longoni A, Haas CB, Torrez VR, Brochier AW, Souza GN, Furtado GV, Gheno TC, Russo A et al. (2017) Peripheral oxidative stress biomarkers in spinocerebellar ataxia type 3/Machado-Joseph disease. Front Neurol 8:485.
|
58 (Symptomatic) 12 (Presymptomatic) |
47 |
Serum |
Symptomatic SCA3/MJD: 335.7 nmol/mg of protein (SE 21.2)*** Presymptomatic individuals: 91.8 nmol/mg of protein (SE 42.2) |
Controls: 182.8 nmol/mg of protein (SE 20.3) |
No |
No |
|
Pacheco et al.,2013Pacheco LS, da Silveira AF, Trott A, Houenou LJ, Algarve TD, Belló C, Lenz AF, Mânica-Cattani MF and da Cruz IB (2013) Association between Machado-Joseph disease and oxidative stress biomarkers. Mutat Res 757:99-103.
|
7 |
7 |
Serum |
172.126(66.49) nmol/mg of protein |
171.606(20.395) nmol/mg of protein |
NA |
NA |
SOD |
de Assis et al., 2017de Assis AM, Saute JAM, Longoni A, Haas CB, Torrez VR, Brochier AW, Souza GN, Furtado GV, Gheno TC, Russo A et al. (2017) Peripheral oxidative stress biomarkers in spinocerebellar ataxia type 3/Machado-Joseph disease. Front Neurol 8:485.
|
58 (Symptomatic) 12 (Presymptomatic) |
47 |
Serum |
Symptomatic: 9.3 (SE 0.5) U/mg of protein * Presymptomatic: 12.3 (SE 1.1) U/mg of protein |
Controls: 10.8 (SE 0.5) U/mg of protein |
No |
No |
GSH-Px |
de Assis et al., 2017de Assis AM, Saute JAM, Longoni A, Haas CB, Torrez VR, Brochier AW, Souza GN, Furtado GV, Gheno TC, Russo A et al. (2017) Peripheral oxidative stress biomarkers in spinocerebellar ataxia type 3/Machado-Joseph disease. Front Neurol 8:485.
|
58 (Symptomatic) 12 (Presymptomatic) |
47 |
Serum |
Symptomatic: 56.3 (SE 2.4) U/mg of protein *** Presymptomatic: 76.8 U/mg of protein (SE 5.2) |
70.3 (SE 2.3) U/mg of protein |
NESSCA R=-0.309* NESSCA = 14.27 (4.7) SE = 0.598 |
No |
Thiol groups |
Pacheco et al., 2013Pacheco LS, da Silveira AF, Trott A, Houenou LJ, Algarve TD, Belló C, Lenz AF, Mânica-Cattani MF and da Cruz IB (2013) Association between Machado-Joseph disease and oxidative stress biomarkers. Mutat Res 757:99-103.
|
7 |
7 |
Serum |
0.112 nmol/mL of erythrocytes (0.032)*** |
0.275 nmol/mL of erythrocytes (0.047) |
NA |
NA |
Catalase |
Pacheco et al., 2013Pacheco LS, da Silveira AF, Trott A, Houenou LJ, Algarve TD, Belló C, Lenz AF, Mânica-Cattani MF and da Cruz IB (2013) Association between Machado-Joseph disease and oxidative stress biomarkers. Mutat Res 757:99-103.
|
7 |
7 |
Serum |
40.7(10.1) mol of H2O2/mL of erythrocytes/min* |
27.67(10.01) mol of H2O2/mL of erythrocytes/min |
NA |
NA |
DNA damage index (comet assay) |
Pacheco et al., 2013Pacheco LS, da Silveira AF, Trott A, Houenou LJ, Algarve TD, Belló C, Lenz AF, Mânica-Cattani MF and da Cruz IB (2013) Association between Machado-Joseph disease and oxidative stress biomarkers. Mutat Res 757:99-103.
|
7 |
7 |
Lymphocytes |
Higher level of DNA damage in SCA3/MJD individuals* (raw values were not presented) |
Higher level of DNA damage in SCA3/MJD individuals* (raw values were not presented) |
NA |
NA |
Others (total polypheno, protein carbonyl, TBARS) |
Pacheco et al., 2013Pacheco LS, da Silveira AF, Trott A, Houenou LJ, Algarve TD, Belló C, Lenz AF, Mânica-Cattani MF and da Cruz IB (2013) Association between Machado-Joseph disease and oxidative stress biomarkers. Mutat Res 757:99-103.
|
7 |
7 |
Serum/Plasma |
Total polyphenols: 0.632 (0.498) mg/mL Protein carbonyl: 2.751 (0.181) nmol/mg protein TBARS: 44.534 (33.01) nmol/mL of erythrocytes |
Total polyphenols: 1.029 (0.770) mg/mL Protein carbonyl: 2.665 (0.471) nmol/mg protein TBARS: 31.786 (32.312) nmol/mL of erythrocytes |
NA |
NA |
Protein quality control systems
|
Beclin-1 |
Nascimento-Ferreira et al., 2011Nascimento-Ferreira I, Santos-Ferreira T, Sousa-Ferreira L, Auregan G, Onofre I, Alves S, Dufour N, Colomer Gould VF, Koeppen A, Déglon N et al. (2011) Overexpression of the autophagic beclin-1 protein clears mutant ataxin-3 and alleviates Machado-Joseph disease. Brain 134:1400-1415.
|
2 |
1 |
Fibroblast (protein) |
Case 1 – 0.86 (0.087) Case 2 – 0.69 (0.05) |
1.15 (0.038) |
NA |
NA |
|
Onofre et al.,2016Onofre I, Mendonça N, Lopes S, Nobre R, de Melo JB, Carreira IM, Januário C, Gonçalves AF and de Almeida LP (2016) Fibroblasts of Machado Joseph Disease patients reveal autophagy impairment. Sci Rep 6:28220.
|
5 |
4 |
Fibroblast- (protein and mRNA) |
Lower Beclin-1 levels in cases .* Raw values were not presented |
Lower Beclin-1 levels in cases.* Raw values were not presented |
NA |
NA |
DNAJB1 |
Zijlstra et al., 2010Zijlstra MP, Rujano MA, Van Waarde MA, Vis E, Brunt ER and Kampinga HH (2010) Levels of DNAJB family members (HSP40) correlate with disease onset in patients with spinocerebellar ataxia type 3. Eur J Neurosci 32:760-770.
|
22 |
6 |
Fibroblast |
No. Raw values were not presented |
NA |
NA |
NA |
HSPB1 |
Zijlstra et al., 2010Zijlstra MP, Rujano MA, Van Waarde MA, Vis E, Brunt ER and Kampinga HH (2010) Levels of DNAJB family members (HSP40) correlate with disease onset in patients with spinocerebellar ataxia type 3. Eur J Neurosci 32:760-770.
|
22 |
6 |
Fibroblast |
Higher levels in cases*. Raw values were not presented |
NA |
NA |
NA |
HSPA1A and HSPA8 |
Zijlstra et al., 2010Zijlstra MP, Rujano MA, Van Waarde MA, Vis E, Brunt ER and Kampinga HH (2010) Levels of DNAJB family members (HSP40) correlate with disease onset in patients with spinocerebellar ataxia type 3. Eur J Neurosci 32:760-770.
|
22 |
6 |
Fibroblast |
No. Raw values were not presented |
NA |
NA |
NA |