Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine Production in Dopaminergic Neurons: Implications for Parkinson’s Disease

Abstract

Increasing the function of residual dopaminergic neurons in the nigra of PD patients is an important area of research as it may eventually compensate the loss. Although tyrosine hydroxylase (TH) is the rate-limiting enzyme in the dopamine (DA) biosynthesis pathway, there are no effective drugs/molecules to upregulate TH and increase the production of DA in nigral dopaminergic neurons. This study underlines the importance of aspirin in stimulating the expression of TH and increasing the level of DA in dopaminergic neurons. At low doses, aspirin increased the expression of TH and the production of DA in mouse MN9D dopaminergic neuronal cells. Accordingly, oral administration of aspirin increased the expression of TH in the nigra and upregulated the level of DA in striatum of normal C57/BL6 mice and aged A53T α-syn transgenic mice. Oral aspirin also improved locomotor activities of normal mice and A53T transgenic mice. While investigating mechanisms, we found the presence of cAMP response element (CRE) in the promoter of TH gene and the rapid induction of cAMP response element binding (CREB) activation by aspirin in dopaminergic neuronal cells. Aspirin treatment also increased the level of phospho-CREB in the nigra of C57/BL6 mice. The abrogation of aspirin-induced expression of TH by siRNA knockdown of CREB and the recruitment of CREB to the TH gene promoter by aspirin suggest that aspirin stimulates the transcription of TH in dopaminergic neurons via CREB. These results highlight a new property of aspirin in stimulating the TH-DA pathway, which may be beneficial in PD patients. Graphical Abstract ᅟ.

Moxibustion Exerts a Neuroprotective Effect through Antiferroptosis in Parkinson’s Disease

“…TH is very important in early onset of PD, because decreased TH activity and protein expression is a key link of DA deficiency and PD phenotypical expression [41–43]. Jellinger found that PD in the central nervous system are pathologically characterized by accumulation of α -syn Lewy body coatings, loss of TH-positive dopaminergic neurons in SN, and depletion of striatal dopamine [44].…”

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

“…CREB binds to the appropriate sequence in the TH gene promoter, thereby increasing TH transcription [191,192]. Among the mechanisms related to exercise-dependent neuroplasticity, CREB is directly involved in regulating TH expression in PD [193,194]. Increased TH transcription plays a crucial role in exercise-dependent neuroplasticity.…”

Moxibustion Protects Dopaminergic Neurons in Parkinson’s Disease through Antiferroptosis

“…Because the head is the meeting point of Governor Vessel and all Yang meridians, Baihui (GV20) can regulate the yang qi of all Yang meridians [24]. Existing research proves that Baihui improves blood circulation in the brain and enhances memory [31]. erefore, this study chose Baihui as an acupoint.…”