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Elucidating the Role of Schwann Cell Mitochondria in Myelin Maintenance.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Elucidating the Role of Schwann Cell Mitochondria in Myelin Maintenance./
作者:	Della Flora Nunes, Gustavo.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	237 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-09, Section: B.
Contained By:	Dissertations Abstracts International82-09B.
標題:	Biochemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28314746
ISBN:	9798582509059

Elucidating the Role of Schwann Cell Mitochondria in Myelin Maintenance.
Della Flora Nunes, Gustavo.

Elucidating the Role of Schwann Cell Mitochondria in Myelin Maintenance. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 237 p.

Source: Dissertations Abstracts International, Volume: 82-09, Section: B.

Thesis (Ph.D.)--State University of New York at Buffalo, 2021.

This item must not be sold to any third party vendors.

The myelin sheath is a multilamellar lipoproteic structure that surrounds many axons to accelerate the conduction of electrical signals. This structure is made by Schwann cells (SCs) in peripheral nerves and oligodendrocytes in brain/spinal cord. Nonetheless, the cellular mechanisms ensuring that myelin is maintained long-term are still poorly understood. Recently, different studies revealed that perturbations to mitochondrial function and cellular metabolism can lead to peripheral neuropathy, but our understanding of how mitochondrial dysfunction can trigger demyelination is still incomplete. In this thesis, we used conditional gene knockouts to investigate the mechanistic links between mitochondrial damage and myelin loss. First, we ablated the pyruvate dehydrogenase complex (PDC) - an important cornerstone of the energetic metabolism - in SCs and oligodendrocytes. Surprisingly, this did not affect preservation of myelin, suggesting that mitochondrial energy production is not essential for myelin maintenance, and that myelinating glia are not main contributors to the pathogenesis of PDC deficiency. Next, we revealed that deletion of the key mitochondrial organizer Prohibitin 1 (Phb1) in SCs triggers a severe demyelinating peripheral neuropathy. This pathology is likely caused by the extensive mitochondrial damage induced by ablation of Phb1, because demyelination occurs preferentially in cells with apparent mitochondrial loss. Furthermore, we showed that, in response to mitochondrial damage, SCs trigger the integrated stress response (ISR), but, contrary to what was previously suggested, the ISR is not detrimental in this context. In addition, we also implicated mTORC1 and JUN in the demyelination process, and suggested that these pathways may link mitochondrial dysfunction to demyelination. These results solidify the importance of SC mitochondria to maintain nerve homeostasis, advance our understanding of the SC response to mitochondrial damage, and indicate that part of this response is directly accountable for the demyelination observed in this context.

ISBN: 9798582509059Subjects--Topical Terms:

518028
Biochemistry.
Subjects--Index Terms:

Demyelination

Elucidating the Role of Schwann Cell Mitochondria in Myelin Maintenance.
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245 1 0 $a Elucidating the Role of Schwann Cell Mitochondria in Myelin Maintenance.
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300 $a 237 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-09, Section: B.
500 $a Advisor: Feltri, M. Laura.
502 $a Thesis (Ph.D.)--State University of New York at Buffalo, 2021.
506 $a This item must not be sold to any third party vendors.
520 $a The myelin sheath is a multilamellar lipoproteic structure that surrounds many axons to accelerate the conduction of electrical signals. This structure is made by Schwann cells (SCs) in peripheral nerves and oligodendrocytes in brain/spinal cord. Nonetheless, the cellular mechanisms ensuring that myelin is maintained long-term are still poorly understood. Recently, different studies revealed that perturbations to mitochondrial function and cellular metabolism can lead to peripheral neuropathy, but our understanding of how mitochondrial dysfunction can trigger demyelination is still incomplete. In this thesis, we used conditional gene knockouts to investigate the mechanistic links between mitochondrial damage and myelin loss. First, we ablated the pyruvate dehydrogenase complex (PDC) - an important cornerstone of the energetic metabolism - in SCs and oligodendrocytes. Surprisingly, this did not affect preservation of myelin, suggesting that mitochondrial energy production is not essential for myelin maintenance, and that myelinating glia are not main contributors to the pathogenesis of PDC deficiency. Next, we revealed that deletion of the key mitochondrial organizer Prohibitin 1 (Phb1) in SCs triggers a severe demyelinating peripheral neuropathy. This pathology is likely caused by the extensive mitochondrial damage induced by ablation of Phb1, because demyelination occurs preferentially in cells with apparent mitochondrial loss. Furthermore, we showed that, in response to mitochondrial damage, SCs trigger the integrated stress response (ISR), but, contrary to what was previously suggested, the ISR is not detrimental in this context. In addition, we also implicated mTORC1 and JUN in the demyelination process, and suggested that these pathways may link mitochondrial dysfunction to demyelination. These results solidify the importance of SC mitochondria to maintain nerve homeostasis, advance our understanding of the SC response to mitochondrial damage, and indicate that part of this response is directly accountable for the demyelination observed in this context.
590 $a School code: 0656.
650 4 $a Biochemistry. $3 518028
650 4 $a Cellular biology. $3 3172791
650 4 $a Neurosciences. $3 588700
653 $a Demyelination
653 $a Mitochondria
653 $a Myelin
653 $a Schwann cell
690 $a 0487
690 $a 0379
690 $a 0317
710 2 $a State University of New York at Buffalo. $b Biochemistry. $3 2091987
773 0 $t Dissertations Abstracts International $g 82-09B.
790 $a 0656
791 $a Ph.D.
792 $a 2021
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28314746