SQSTM1/p62 is a prototype autophagy receptor, which is commonly found in protein aggregates associated with major neurodegenerative diseases. While accumulation of SQSTM1 implicates a disturbance of selective autophagy pathway, the pathogenic mechanism that contributes to impaired autophagy degradation remains poorly characterized.

Sequestosome 1/p62 Protein in Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration SQSTM1 /p62, henceforth referred to as p62, is a scaffold protein that has roles in various signaling pathways and protein degradation.

2022年8月25日 · Our data demonstrate co-deposition of p62 with mutant and wild-type disSOD1 and phosphorylated TDP-43 in familial and sporadic ALS spinal cord motor neurons, consistent with attempts by p62 to mitigate SOD1 and TDP-43 deposition. Wild-type SOD1 and TDP-43 co-deposition was also frequently observed in ALS cases lacking SOD1 mutations.

2021年6月1日 · We found that stressors (proteasome inhibition and arsenic) increased p62 expression and that this shifted the nuclear:cytoplasmic TDP-43 ratio. Overall, our study suggests that environmental...

The results show that p62 accumulated in protein aggregates in G93A transgenic mice long before the disease onset, suggesting that p62 may be involved in the mutant SOD1-mediated ALS etiology. The p62 mRNA levels in the spinal cords of WT and G93A transgenic mice were measured by quantitative RT-PCR.

2022年5月1日 · Mutations in the functional domains of p62 provide links to the pathogenetic mechanisms of p62 and dyshomeostasis of p62 levels is noted in several types of ALS and FTD. We present here that the dysregulated ALS and FTD signaling pathways are linked, with p62 converging the molecular mechanisms.

We present here that the dysregulated ALS and FTD signaling pathways are linked, with p62 converging the molecular mechanisms. This review summarizes the current literature on the complex role of p62 in the pathogenesis across the ALS/FTD spectrum.

Mutations in SQSTM1 encoding the sequestosome 1/p62 protein have recently been identified in familial and sporadic cases of amyotrophic lateral sclerosis (ALS). p62 is a component of the ubiquitin inclusions detected in degenerating neurons in ALS patients.

Molecular chaperones, the UPS, and the autophagy-lysosome system function to monitor protein quality and protect cells from dysfunctional, malfolded or denatured proteins. The presence of ubiquitin, p62 and molecular chaperones in ALS aggregates implicates a role for all these three systems in ALS pathophysiology (Fig. 2).

SQSTM1/p62 是一种原型自噬受体，常见于与主要神经退行性疾病相关的蛋白质聚集体中。 虽然 SQSTM1 的积累涉及选择性自噬途径的紊乱，但导致自噬降解受损的致病机制仍然难以表征。 在此，我们表明肌萎缩侧索硬化症 （ALS） 和 TBK1 和 SQSTM1 的额颞叶变性 （FTLD） 相关突变破坏选择性自噬并引起神经毒性。 我们的数据表明，蛋白毒性应激激活丝氨酸/苏氨酸激酶 TBK1，TBK1 与自噬激酶 ULK1 协调，促进 UBA 结构域自噬受体 SQSTM1 的协同磷酸化和选 …