TMEM55B downregulation promotes neurodegeneration in Alzheimer disease models.

Lysosomal function plays a vital role in various cellular processes like protein degradation, cholesterol regulation, and cell invasion. Alterations in lysosome position and movement can lead to disorders like neurodegeneration and cancer. This study reveals the importance of Transmembrane Protein 55B (TMEM55B) in causing neurodegeneration.

Researchers used human data, genetically modified flies, and induced pluripotent stem cell-derived neurons to explore this connection. They discovered that lowering TMEM55B levels exacerbates neuronal damage in Alzheimer's disease. The presence of excessive lysosomes in neuronal axons, enhanced Tau-related retinal damage, impaired movement, early death, and cell demise were observed in these AD models.

Similarly, iPSC-derived AD neurons displayed decreased TMEM55B levels, hindered autophagic processes, and greater amounts of phosphorylated Tau within lysosomes, supporting the findings from the fly experiments. The study suggests that TMEM55B downregulation may contribute to neurodegeneration by disrupting lysosomal transport, which may impede the clearance of Tau from neurons.

The findings are crucial for confirming the role of lysosomal proteins in preserving healthy neurons and maintaining normal lysosomal function. This work highlights the need for further investigation into lysosome-related neurodegeneration and could lead to potential treatments for lysosome-associated neuronal disorders.