Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of Beclin 1-Dependent Autophagy

Cheng, Xiao; Li, Si Yue; Mao, Cheng Jie; Wang, Mei Xia; Chen, Jing; Wang, Fen; Wang, Guang Hui; Deng, Wenbin; Li, Xiao Kang; Liu, Chun‐Feng

doi:10.1016/j.neuroscience.2017.11.040

Cited by 8 publications

(2 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this also implies that other TFs such as CREB- ( 57 ) or SRF-directed IEGs known to regulate autophagy ( 58 , 59 ) might provide a link between neuronal activity and autophagy gene regulation. So far, only 2 instances of an SRF connection with autophagy have been reported ( 60 , 61 ). Here, SRF protected MNs from rotenone-induced cellular death and reduced synuclein aggregation; however, this beneficial effect was abolished by either Beclin1 or Atg5 knockdown, implying that autophagy induction is a critical component of the neuroprotective SRF effects ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

“…So far, only 2 instances of an SRF connection with autophagy have been reported ( 60 , 61 ). Here, SRF protected MNs from rotenone-induced cellular death and reduced synuclein aggregation; however, this beneficial effect was abolished by either Beclin1 or Atg5 knockdown, implying that autophagy induction is a critical component of the neuroprotective SRF effects ( 60 ). This cell culture finding supports our conclusion that, in response to neuronal activity, SRF modulates autophagy to convey neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

SRF deletion results in earlier disease onset in a mouse model of amyotrophic lateral sclerosis

Song,

Dikwella,

Sinske

et al. 2023

JCI Insight

View full text Add to dashboard Cite

Changes in neuronal activity modulate the vulnerability of motoneurons (MNs) in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). So far, the molecular basis of neuronal activity’s impact in ALS is poorly understood. Herein, we investigated the impact of deleting the neuronal activity–stimulated transcription factor (TF) serum response factor (SRF) in MNs of SOD1 G93A mice. SRF was present in vulnerable MMP9 + MNs. Ablation of SRF in MNs induced an earlier disease onset starting around 7–8 weeks after birth, as revealed by enhanced weight loss and decreased motor ability. This earlier disease onset in SRF-depleted MNs was accompanied by a mild elevation of neuroinflammation and neuromuscular synapse degeneration, whereas overall MN numbers and mortality were unaffected. In SRF-deficient mice, MNs showed impaired induction of autophagy-encoding genes, suggesting a potentially new SRF function in transcriptional regulation of autophagy. Complementary, constitutively active SRF-VP16 enhanced autophagy-encoding gene transcription and autophagy progression in cells. Furthermore, SRF-VP16 decreased ALS-associated aggregate induction. Chemogenetic modulation of neuronal activity uncovered SRF as having important TF-mediating activity–dependent effects, which might be beneficial to reduce ALS disease burden. Thus, our data identify SRF as a gene regulator connecting neuronal activity with the cellular autophagy program initiated in degenerating MNs.

show abstract