Table 2.
The role of PIP species in different neuroinflammatory conditions.
| Disease | PIP Species | Suspected roles in pathology | References |
|---|---|---|---|
| Alzheimer’s disease | PI(4)P | Key role in uptake systems including phagocytosis. | Stokes and Hawthorne (1987), Wu et al. (2006), Levin et al. (2017) and Zhang et al. (2017) |
| PI(3,4)P2 | Mutations in the PI(3,4)P2 synthesis enzyme INPP5D increase genetic AD risk. Excess PI3K (generates PI(3,4)P2) activity in AD. | Lambert et al. (2013), Hawkins and Stephens (2016) and Jing et al. (2016) | |
| PI(4,5)P2 | A genetic variant in PLCγ2, which breaks down PI(4,5)P2, protects against AD2, acts as a risk factor for AD. | McIntire et al. (2012) and Sims et al. (2017) | |
| PI(3,4,5)P3 | Excess PI3K (generates PI(3,4,5)P3) activity in AD. | Heras-Sandoval et al. (2014) | |
| Parkinson’S disease | PI(4,5)P2 | Reduced PLC activity and PI(4,5)P2 metabolism in PD cortex, perhaps following the accumulation of α-synuclein which appears to inhibit PLC enzymes. Increased PI(4,5)P2 in PD patient substantia nigra. | Sekar and Taghibiglou (2018) |
| PI(3,4,5)P3 | Excess PI3K (generates PI(3,4,5)P3) reduced activity in PD3) increased in PD. | Bernier et al. (2013b), Sekar and Taghibiglou (2018) and Katan and Cockcroft (2020) | |
| Huntington’S disease | PI(3)P | Inhibiting PIP-4 kinase (phosphorylates PI(3)P) reduces mHTT and rescues neurodegeneration in HD drosophila. | Al-Ramahi et al. (2017) |
| PI(5)P | Inhibiting PIP-4 kinase (phosphorylates PI(5)P) reduces mHTT and rescues neurodegeneration in HD drosophila. | Al-Ramahi et al. (2017) | |
| Amyotrophic lateral sclerosis | PI(4)P | ALS risk gene VAPB is proposed to affect neurite extension during differentiation via regulation of PI(4)P distribution. | Genevini et al. (2019) |
| PI(3,5)P2 | Non-synonymous variants in the PI(3,5)P2 phosphatase FIG4 found in 1–2% of ALS patients. LOF leads to reduced levels of PI(3,5)P2 and is suspected to affect autophagy. | Chow et al. (2007, 2009) and Nguyen et al. (2019) |
Aβ, amyloid β; AD, Alzheimer’s disease; INPP5D, Src homology 2 (SH2) domain containing inositol polyphosphatase 5-phosphatase 1; PLCγ2, phospholipase C γ 2; SYNJ1, synaptojanin 1; PD, Parkinson’s disease; PTEN, phosphatase and tensin homolog; mHTT, mutated Huntington protein; HD, Huntington’s disease; ALS, amyotrophic lateral sclerosis; VAPB, vesicle-associated membrane protein-associated protein B; FIG4, Factor induced gene 4; LOF, loss of function.