Disrupted mannosidase enzymes in C9orf72 ALS/FTD

Reduced Golgi mannosidase enzymes MAN1A1 and MAN1A2 are identified in ALS-associated microglia and astrocytes, linking disrupted glycan processing to ALS pathology.

• Why it matters: ALS involves neuroinflammation, but the non-neuronal mechanisms in glial cells remain incompletely defined, limiting targets beyond motor neurons.
• What they did: The study analyzed human postmortem tissue and an iPSC-derived glia-crosstalk model, measuring glycan-related enzyme levels in ALS-associated microglia and astrocytes.
• The result: Lower MAN1A1 and MAN1A2, alongside other glycan enzymes, is linked to inflammation and related ALS mechanisms such as lysosomal proteostasis defects, extracellular matrix changes, disrupted secretion, and altered cell-cell signaling.

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