More than a marker: potential pathogenic functions of MAP2

Abstract

Microtubule-associated protein 2 (MAP2) is the predominant cytoskeletal regulator within neuronal dendrites, abundant and specific enough to serve as a robust somatodendritic marker. It influences microtubule dynamics and microtubule/actin interactions to control neurite outgrowth and synaptic functions, similarly to the closely related MAP Tau. Though pathology of Tau has been well appreciated in the context of neurodegenerative disorders, the consequences of pathologically dysregulated MAP2 have been little explored, despite alterations in its immunoreactivity, expression, splicing and/or stability being observed in a variety of neurodegenerative and neuropsychiatric disorders including Huntington's disease, prion disease, schizophrenia, autism, major depression and bipolar disorder. Here we review the understood structure and functions of MAP2, including in neurite outgrowth, synaptic plasticity, and regulation of protein folding/transport. We also describe known and potential mechanisms by which MAP2 can be regulated via post-translational modification. Then, we assess existing evidence of its dysregulation in various brain disorders, including from immunohistochemical and (phospho) proteomic data. We propose pathways by which MAP2 pathology could contribute to endophenotypes which characterize these disorders, giving rise to the concept of a "MAP2opathy"-a series of disorders characterized by alterations in MAP2 function.

Association of region‐specific hippocampal reduction of neurogranin with inflammasome proteins in post mortem brains of Alzheimer's disease

“…NFTs accumulate in the entorhinal cortex, the subiculum, and in CA1 of the hippocampal region, 1,2 in the control cases, demonstrating age‐related neuropathological changes. Although the rate of p‐tau accumulation and the degree of destabilization of MAP2 occur independently, 29 it is thought that as NFTs increase, MAP2 destabilizes, the neurons lose plasticity, and neuronal atrophy will follow 18 . Here we assessed the change in the number of MAP2‐positive neurons in the hippocampus and entorhinal cortex.…”

“…The microtubule‐associated proteins (MAPs) of type II (MAP2) stabilize the dendrites and the axons of neurons. Studies show that p‐tau is mislocated to dendritic spines leading to microtubule destabilization and synaptic dysfunction 17–20 . In addition, synaptic loss is reported to be associated with microglia‐mediated neuroinflammation in AD 21,22 …”

Tunable hydrogel viscoelasticity modulates human neural maturation

“…Lastly, mature neurons are characterized by the expression of microtubule-associated protein 2 (MAP2), which stabilizes microtubules in the dendrites, and RNA binding fox-1 homolog 3 (RBFOX3), a neural-specific pre-mRNA alternative splicing regulator that also produces the widely used neuronal nuclei antigen ( 61 , 62 ). As with the expression of TUBB3 , the expression of both MAP2 and RBFOX3 was significantly increased in cells encapsulated within both DYN gels compared to those in Static gels (Fig.…”

Myricetin attenuates hypoxic-ischemic brain damage in neonatal rats via NRF2 signaling pathway

“…The quantitative results of residual brain volume showed that compared with Sham group, the brain atrophy was obvious in HI group, and myricetin treatment could significantly alleviate the degree of brain atrophy in HI-induced rats ( Figure 2B ). Microtubule-associated protein-2 (MAP-2) is the main cytoskeletal regulator within neuronal dendrites that serves as a robust somatodendritic marker ( DeGiosio et al, 2022 ). Myelin basic protein (MBP) is a key component of myelin sheath in the central nervous system that serves as an oligodendrocyte marker ( Harauz et al, 2004 ).…”