However, human neuropathological studies are not yet available. Owing to the large LMTK2 interactome it is not surprising that the protein is implicated in several vital physiological functions and diseases (Table 1) including AD 15. It has important interacting partners such as CDK5/p35 complex, catalytic subunit of Protein Phosphatase 1 (PP1C), cystic fibrosis transmembrane conductance regulator (CFTR) and myosin VI. LMTK2 is a member of the membrane-anchored protein kinase family 14. identified the Lemur tyrosine kinase 2 (LMTK2) as the missing link of the signalling pathway between the two above mentioned tau-kinases 13. Moreover, CDK5 can suppress the activity of GSK3β indirectly, but the precise mechanism behind this observation was unknown until Manser et al. Cyclin-dependent kinase 5 (CDK5) and Glycogen synthase kinase-3β (GSK3β) are two major tau-kinases. Despite the crucial role of tau hyperphosphorylation in the pathogenesis the initiative event leading to pathological activity of numerous kinases remains to be elucidated. NFT burden inversely correlates with the number of surviving neurons, suggesting that neurofibrillary lesions have key role in degenerative changes and apoptotic cell loss 12. Under pathological circumstances the hyperphosphorylated tau 10 is prone to self-aggregation and toxic through sequestering normal tau and other microtubule associated proteins resulting in microtubule disassembly 11. Tau is involved in a myriad of physiological cellular functions such as stabilization of microtubules, axonal transport, synaptic transmission or activation of unfolded protein response 6, 7, 8, 9. The major component of NFT is hyperphosphorylated microtubule-associated protein tau. Although, neocortical LBD is an α-synucleinopathy characterized by the pathological aggregation and intracellular deposition of α-synuclein forming Lewy bodies and Lewy neurites, coexisting AD-type NFT pathology is also frequently observed. Neuropathological hallmarks of AD are the deposition of extracellular β-amyloid plaques and intracellularly aggregated neurofibrillary tangles (NFTs) 5. In order to develop more efficient disease-modifying treatments, the molecular, biochemical and genetic alterations (‘omics’) should be better explored 2, 3, 4. Alzheimer’s disease (AD) and neocortical Lewy body disease (LBD) are the most common causes of dementia accounting for 75–80 percent of the cases 1. We provide neuropathological evidence on decreased neuronal LMTK2 immunolabelling in AD, with implications for pathogenesis.ĭementias are challenging health issues in our aging society. The moderate decrease in neocortical LBD suggests the effect of coexisting AD pathology. There was significant difference between the mean grey values of CNT vs. Mean grey values were calculated for each group after measuring the grey scale LMTK2 signal intensity of each individual neuron. Digital image analysis was performed to measure the average immunopositivity of groups. Neurons, including tau-positive tangle-bearing ones, showed decreased chromogenic and immunofluorescent labelling in AD in every cortical layer compared to CNT and neocortical LBD. LMTK2 immunopositivity was limited to the neuronal cytoplasm.
Herewith a neuropathological characterization is presented in AD and neocortical LBD samples using chromogenic and fluorescent LMTK2 immunohistochemistry on post-mortem brain tissues and compared them to age-matched controls (CNTs). Lemur tyrosine kinase 2 (LMTK2) is involved in several physiological and pathological cellular processes. Elucidating pathomechanism and identifying novel therapeutic targets are of paramount importance. Alzheimer’s disease (AD) and neocortical Lewy body disease (LBD) are the most common neurodegenerative dementias, with no available curative treatment.
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