Table 2 Proposed physiological roles of cellular prion protein

Synaptic transmission and plasticity

Reduced long-term potentiation

[58] (ZH1)

[29] (Edgb)

[61] (ZH1, other ^a)

[98] (ZH1)

Reduced excitatory and inhibitory synaptic transmission

[58] (ZH1)

[62] (ZH1, Ngsk)

[61] (ZH1, other ^a)

[147] (ZH1)

Memory formation

Reduced spatial learning and memory

[64] (other ^b)

[28] (ZH1)

Reduced avoidance learning and memory

[65] (ZH1)

[148] (Ngsk)

[68] (ZH1)

Stabilization of sleep and circadian rhythm

Altered circadian rhythm, increased sleep fragmentation, increased SWA after sleep deprivation

[71] (ZH1, Edgb)

[74] (Other ^b)

Neuronal excitability

Reduced Kv4.2 currents

[77] (ZH1, HEK293T)

Reduced sAHP and calcium-activated potassium currents

[79] (ZH1)

[80] (ZH1)

[82] (ZH1)

[39] (Tg35)

[83] (ZH1)

Increased susceptibility to Kainate-induced seizures

[84] (ZH1)

[41] (Other ^b)

Calcium homeostasis

Reduced VGCC currents

[80] (ZH1)

[83] (ZH1)

Increased calcium buffering

[83] (ZH1)

Glutamate receptor function

Increased NMDA currents, nociception and depressive-like behavior

[90] (ZH1)

[91, 92] (ZH1)

Upregulation of Kainate receptor subunits

[84] (ZH1)

Neurite outgrowth

Delayed development of cerebellar circuitry

[120] (ZH1)

Reduced neurite outgrowth in vitro

[106] (ZH1)

Toxicity elicited by oligomeric species

Protected from LTP reduction induced by toxic Aβ species

[98] (ZH1, other ^c)

[102] (ZH1)

[103] (ZH1)

[104] (Other ^b)

[105] (Other ^a)

Neuroprotection

Larger lesions in model of acute cerebral ischemia

[122] (ZH1)

[123] (ZH1)

[124] (ZH1)

Decreased SOD activity

[133] (ZH1)

[135] (ZH1)

Copper, zinc, iron, and lactate metabolism

Reduced zinc content in primary neurons

[95] (ZH1, SH-SY5Y)

Increased lactate-uptake in cultured astrocytes

[96] (ZH1)

Altered iron and copper metabolism

[139] (Other ^a)

Peripheral myelin maintenance

Age-dependent demyelinating neuropathy

[141] (ZH1, Edgb)

[42] (ZH3)