NEU1—A Unique Therapeutic Target for Alzheimer’s Disease

Abstract

Neuraminidase 1 (NEU1) is considered to be the most abundant and ubiquitous mammalian enzyme, with a broad tissue distribution. It plays a crucial role in a variety of cellular mechanisms. The deficiency of NEU1 has been implicated in various pathological manifestations of sialidosis and neurodegeneration. Thus, it is a novel therapeutic target for neurodegenerative changes in the Alzheimer’s brain. However, to manipulate NEU1 as a therapeutic target, it is imperative to understand that, although NEU1 is commonly known for its lysosomal catabolic function, it is also involved in other pathways. NEU1 is involved in immune response modulation, elastic fiber assembly modulation, insulin signaling, and cell proliferation. In recent years, our knowledge of NEU1 has continued to grow, yet, at the present moment, current data is still limited. In addition, the unique biochemical properties of NEU1 make it challenging to target it as an effective therapeutic option for sialidosis, which is a rare disease but has an enormous patient burden. However, the fact that NEU1 has been linked to the pathology of Alzheimer’s disease, which is rapidly growing worldwide, makes it more relevant to be studied and explored. In the present study, the authors have discussed various cellular mechanisms involving NEU1 and how they are relevant to sialidosis and Alzheimer’s disease.

Unveiling the Impact of Endogenous Sialidases on Human Non-Infectious Disease Pathogenesis

“…Likewise, alterations in sialylation patterns have been observed in both neurological disorders and the microglia's inflammatory response (Minami et al, 2017;Annunziata et al, 2013). Khan et al (2021) found that Neu1 deficiency can cause an amyloidogenic process similar to Alzheimer's Disease (AD) in mice (Khan et al, 2021;Khan and Sergi, 2022). In this disease, Neu1 desialylates macrophage and dendritic cell surface receptors and activates phagocytosis.…”

Neuraminidase 1 promotes renal fibrosis development in male mice

“…Fourth, we also reported that neuraminidases activation resulted in accumulation of circulating N -acetyl-neuraminic acid, a signaling metabolite that can trigger RhoA and Cdc42-dependent myocardial injury 21 . On account of their various functions, mammalian neuraminidases have been shown to play an emerging role in several human diseases, including autoimmune 22 , 23 , cardiovascular diseases 20 , 24 , 25 cancers 26 , neurodegenerative disorders 27 , and lung diseases 28 , 29 . Design of the specific inhibitors targeting neuraminidases have the potential to treat these diseases 30 , 31 .…”