Table A.17.

Response–Response and temporality concordance table

Concentration at the target site, in‐vitro	MIE	KE1 Mitochondrial ROS production and dysfunction	KE2 Impaired proteostasis	KE3 Degeneration of DA neurons of nigrostriatal pathway	AO Parkinsonian motor symptoms
10 μM [1, 10, 12]	No data	± (at 24 h)	+ (ALP 6 h, time‐dependent at 24 h)	± (at 24 h)
20 10 to 50 μM [1, 2, 10]	No data	+ (at 6 and 24 h; ne 3 h)	+ (UPS at 6 h)	+ (at 24 h)
50–200 μM [1, 2, 8, 10, 13]	++ (at 24 and 48 h)	++ (at 6 and 24 h)	++ (UPS at 6 h)	++ (at 24 and 48 h)
200 μM to 1 mM [3, 4, 7, 8, 9, 10, 12]	+++ (at 4, 6, 24 and 48 h)	++ (at 4 and 6 h) +++ (at 24 h)	+++ (UPS at 48 h) ++ (ALP at 24 h)	++/+++ (at 18, 24 and 48 h)
Concentration at the target site, in vivo	MIE	KE1 Mitochondrial dysfunction (ROS production)	KE2 Impaired proteostasis	KE3 Degeneration of DA neurons of nigrostriatal pathway	AO Parkinsonian motor symptoms
Below 3 μM [15, 16]	+ (4 weeks)	Increase activity in ROS‐scavenging enzymes + (4 week)	No data	Decrease in number of TH+ in SN ± (at 4 week)	No locomotor deficit
About 3–10 μM [6,5, 13,14, 15]	++ weeks)	Increased lipid peroxidation  − (1 week)  ++/+++ (2 week)  +++ (6–9 week) Increase activity in ROS‐scavenging enzymes (4 week)  ++	Impaired proteostasis and autophagy  ++	Decrease in number of TH+ in SN  − (1 week)  + (at 2–4 week)	Locomotor deficit ± (at 2–4 week)

González‐Polo 2007 [1]; Ding and Keller, 2001 [2]; Yang and Tiffany‐Castiglioni, 2007 [3]; Cantu 2011 [4]; Breckenridge 2013 [5]; Prasad 2007 and 2009 [6]; Huang 2012 [7]; Lopert 2012 [8] *LDH as % of control and not of maximal release; Chau 2009 [9]; de Oliveira 2016 [10]; Garcia‐Garcia 2013 [11]; Rodriguez‐Rocha 2013 [12]; Patel 2006 [13]; McCormack 2005 [14]; Mitra et al. 2011 [15]; Brooks et al. 1999 [16].

+, ++, +++ are intended only to demonstrate intra and inter KEs relationship.