• Modeling Mechanism：

  MPTP hydrochloride is metabolized in vivo to produce the active product 1-methyl-4-phenylpyridine ion (MPP⁺), which induces PD pathology through multiple mechanisms: ① MPP⁺ is selectively taken up by the dopamine transporter (DAT), inhibiting the activity of mitochondrial complex I in dopaminergic neurons of the substantia nigra pars compacta (SNc), leading to oxidative stress and energy metabolism disorders; ② It activates the non-receptor tyrosine kinase c-Abl, phosphorylating it at the Y245 site, which in turn phosphorylates p38α (Y182, Y323 sites), promoting p38α dimerization and activation, and initiating the neuronal apoptosis pathway; ③ It leads to the death of SNc dopaminergic neurons and damage to striatal dopaminergic nerve endings, resulting in motor dysfunction.

• Related Products：

  MPTP hydrochloride (T4081)

• Modeling Method：

  Experimental Subject：Mice: C57BL/6J, c-Abl conditional knockout mice (c-Ablⁿˣ/ˣ; CaMKIIα-iCre⁺/⁻); adult

  Dosage and Administration Route：① Core modelling: MPTP hydrochloride (20 mg/kg), dissolved in physiological saline, intraperitoneal injection (i.p.); ② Control treatment: equal volume saline solution administered via identical route; ③ Intervention validation (optional): - c-Abl inhibitor STI571 (30 mg/kg) – intraperitoneal injection – administered four times starting one day prior to modelling, with one-day intervals, plus an additional dose 12 hours post-modelling; - p38α inhibitor SB203580 (5 mg/kg) · intraperitoneal injection · dosing regimen identical to STI571

  Dosing Frequency and Duration Model：Four doses administered at 2-hour intervals

• Validation：

  Behavioral indicators: Motor function: The fall latency in the rotarod test was significantly shortened in the model group (P<0.05 vs. control group). STI571 or SB203580 intervention significantly prolonged the latency and improved motor coordination. Pathological indicators: Neuronal damage: SNc tyrosine hydroxylase (TH) positive neurons decreased by about 40%, Nissl staining confirmed neuronal death, and striatal TH protein expression was significantly downregulated. c-Abl knockout or inhibitor intervention could salvage the loss of TH positive neurons. Molecular indicators: Signaling pathway activation: c-Abl Y245 phosphorylation level increased from 2 hours after modeling, and the peak phosphorylation level of p38α T180/Y182 appeared 3 days after modeling. c-Abl knockout or inhibitor could block p38α activation. Specificity verification: The striatal MPP⁺ level was significantly increased after modeling (HPLC detection), and c-Abl or p38α... The inhibitor does not affect MPP⁺ generation, confirming its protective effect by regulating downstream signaling pathways.

*Precautions： The animals were euthanized 7 days after the last MPTP injection.

*References：Wu R,et,al. c-Abl-p38α signaling plays an important role in MPTP-induced neuronal death. Cell Death Differ. 2016 Mar;23(3):542-52.