New brain atlas of lysosomal proteins could help researchers studying neurological disease

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"In brief

• Stanford researchers created the first atlas of lysosomal proteins in the brain, crucial for understanding neurodegenerative diseases.
• The atlas highlights links between lysosomal dysfunction and disorders like Alzheimer’s and Parkinson’s, guiding potential therapeutic developments.
• The data is publicly accessible, promoting global collaboration and exploration of lysosomal roles in neurological conditions.

...

“Lysosomal function is essential for brain health, and mutations in lysosomal genes are risk factors for neurodegenerative diseases,” ..."

From the highlights and abstract:

"Highlights

• Lysosomal proteomics of brain cell types

• Identification of previously uncharacterized and cell-type-specific lysosomal proteins

• SLC45A1 is a neuron-specific lysosomal sugar transporter

• SLC45A1 loss drives lysosomal and mitochondrial dysfunction

Summary

Mutations in lysosomal genes cause neurodegeneration and neuronopathic lysosomal storage disorders (LSDs). Despite their essential role in brain homeostasis, the cell-type-specific composition and function of lysosomes remain poorly understood.

Here, we report a quantitative protein atlas of lysosomes from mouse neurons, astrocytes, oligodendrocytes, and microglia. We identify dozens of proteins not previously annotated as lysosomal and reveal the diversity of lysosomal composition across brain cell types.

Notably, we identified SLC45A1, a gene whose mutations cause a monogenic neurological disease, as a neuron-specific lysosomal protein.

Loss of SLC45A1 causes lysosomal dysfunction in vitro and in vivo. SLC45A1 functions as a lysosomal sugar transporter and impacts the stability of the V1 subunits of the vacuolar ATPase (V-ATPase). Consistently, SLC45A1 loss reduces lysosomal V1 subunits, elevates lysosomal pH, and disrupts iron homeostasis, causing mitochondrial dysfunction. Altogether, our work redefines SLC45A1-associated disease as an LSD and establishes a comprehensive map to study lysosome biology at cell-type resolution."

New atlas could help researchers studying neurological disease | Stanford Report "A database of lysosomal proteins is already guiding researchers in studying how brain cells’ waste and recycling systems work – or don’t – in Alzheimer’s and other neurological diseases."

Cell-type resolved protein atlas of brain lysosomes identifies SLC45A1-associated disease as a lysosomal disorder (open access)

Lysosomal Brain Protein Atlas

Graphical abstract