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Relation of hippocampal phospho-SAPK/JNK granules in Alzheimer's disease and tauopathies to granulovacuolar degeneration bodies.
Acta Neuropathol 2007; 113(1):63-73AN

Abstract

Protein misfolding is a distinguishing feature of a number of neurodegenerative diseases. Accumulation of misfolded protein often results in cellular lesions, the location of lesions correlating with the nature of symptoms. Alzheimer's disease (AD), Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD) and Pick's Disease (PiD) all present with pathological lesions containing hyperphosphorylated filamentous tau protein; however, the location and type of lesion varies. In addition, granulovacuolar degeneration (GVD) bodies have been reported within hippocampal pyramidal neurons in AD, PSP, CBD and PiD tissue. GVDs are defined as electron-dense granules within double membrane-bound cytoplasmic vacuoles. We have previously reported that the phosphorylated form of stress-activated protein kinase/c-Jun N-terminal kinase (p-SAPK/JNK) accumulates in granules within hippocampal pyramidal cell bodies in AD tissue at the time that hyperphosphorylated tau begins to aggregate into early-stage NFTs. We now report that p-SAPK/JNK granules are found within the hippocampal CA1 region of PSP, CBD and PiD cases as well and that these granules are likely GVD bodies. Quantitatively, p-SAPK/JNK granules and GVDs are found in comparable numbers of CA1 cells. Within cells, p-SAPK/JNK granules are distributed throughout the cytoplasm in a manner similar to the distribution of GVDs and a subset of granules co-localize with GVD markers. Ultrastructurally, p-SAPK/JNK granules are located in large cytoplasmic vacuoles, thereby fitting the definition of a GVD body. With the implication of granular p-SAPK/JNK as a marker of GVDs, our study strongly suggests that a heterogeneous group of proteins form GVDs. The mechanism of GVD formation is therefore an interesting one, and is likely separate and distinct from the mechanism of tau inclusion formation.

Authors+Show Affiliations

Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL 60611, USA. s-lagalwar@northwestern.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17089132

Citation

Lagalwar, Sarita, et al. "Relation of Hippocampal phospho-SAPK/JNK Granules in Alzheimer's Disease and Tauopathies to Granulovacuolar Degeneration Bodies." Acta Neuropathologica, vol. 113, no. 1, 2007, pp. 63-73.
Lagalwar S, Berry RW, Binder LI. Relation of hippocampal phospho-SAPK/JNK granules in Alzheimer's disease and tauopathies to granulovacuolar degeneration bodies. Acta Neuropathol. 2007;113(1):63-73.
Lagalwar, S., Berry, R. W., & Binder, L. I. (2007). Relation of hippocampal phospho-SAPK/JNK granules in Alzheimer's disease and tauopathies to granulovacuolar degeneration bodies. Acta Neuropathologica, 113(1), pp. 63-73.
Lagalwar S, Berry RW, Binder LI. Relation of Hippocampal phospho-SAPK/JNK Granules in Alzheimer's Disease and Tauopathies to Granulovacuolar Degeneration Bodies. Acta Neuropathol. 2007;113(1):63-73. PubMed PMID: 17089132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relation of hippocampal phospho-SAPK/JNK granules in Alzheimer's disease and tauopathies to granulovacuolar degeneration bodies. AU - Lagalwar,Sarita, AU - Berry,Robert W, AU - Binder,Lester I, Y1 - 2006/11/07/ PY - 2006/07/10/received PY - 2006/10/12/accepted PY - 2006/09/26/revised PY - 2006/11/8/pubmed PY - 2007/10/30/medline PY - 2006/11/8/entrez SP - 63 EP - 73 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 113 IS - 1 N2 - Protein misfolding is a distinguishing feature of a number of neurodegenerative diseases. Accumulation of misfolded protein often results in cellular lesions, the location of lesions correlating with the nature of symptoms. Alzheimer's disease (AD), Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD) and Pick's Disease (PiD) all present with pathological lesions containing hyperphosphorylated filamentous tau protein; however, the location and type of lesion varies. In addition, granulovacuolar degeneration (GVD) bodies have been reported within hippocampal pyramidal neurons in AD, PSP, CBD and PiD tissue. GVDs are defined as electron-dense granules within double membrane-bound cytoplasmic vacuoles. We have previously reported that the phosphorylated form of stress-activated protein kinase/c-Jun N-terminal kinase (p-SAPK/JNK) accumulates in granules within hippocampal pyramidal cell bodies in AD tissue at the time that hyperphosphorylated tau begins to aggregate into early-stage NFTs. We now report that p-SAPK/JNK granules are found within the hippocampal CA1 region of PSP, CBD and PiD cases as well and that these granules are likely GVD bodies. Quantitatively, p-SAPK/JNK granules and GVDs are found in comparable numbers of CA1 cells. Within cells, p-SAPK/JNK granules are distributed throughout the cytoplasm in a manner similar to the distribution of GVDs and a subset of granules co-localize with GVD markers. Ultrastructurally, p-SAPK/JNK granules are located in large cytoplasmic vacuoles, thereby fitting the definition of a GVD body. With the implication of granular p-SAPK/JNK as a marker of GVDs, our study strongly suggests that a heterogeneous group of proteins form GVDs. The mechanism of GVD formation is therefore an interesting one, and is likely separate and distinct from the mechanism of tau inclusion formation. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/17089132/Relation_of_hippocampal_phospho_SAPK/JNK_granules_in_Alzheimer's_disease_and_tauopathies_to_granulovacuolar_degeneration_bodies_ L2 - https://dx.doi.org/10.1007/s00401-006-0159-4 DB - PRIME DP - Unbound Medicine ER -