Title

Reduced dynamin-related protein 1 protects against phosphorylated Tau-induced mitochondrial dysfunction and synaptic damage in Alzheimer's disease.

Journal

Human molecular genetics

Volume

25

Issue

None

Pages

4881-4897

Date

2016-11-15

Authors

Sesaki H | Fry D | Manczak M | Suneetha Y | Kandimalla R | Reddy PH

Using real-time RT-PCR, immunoblotting and immunostaining analyses, we measured mRNA expressions and protein levels of genes related to the mitochondrial dynamics—Drp1 and Fis1 (fission), Mfn1, Mfn2 and Opa1 (fusion), CypD (matrix), mitochondrial biogenesis—Nrf1, Nrf2, PGC1a and TFAM and synaptic— synaptophysin, PSD95, synapsin 1, synaptobrevin 1, neurogranin, GAP43 and synaptopodin in brain tissues from 6-month old Drp1þ/+-, Tau, TauXDrp1þ/+- and wild-type mice. Decreased mRNA and protein levels of fission and matrix and increased levels of fusion, mitochondrial biogenesis, and synaptic genes were found in 6-month-old TauXDrp1þ/+- mice relative to Tau mice. Mitochondrial dysfunction was reduced in TauXDrp1þ/+- mice relative to Tau mice.

Mitochondrial dysfunction found to be reduced in TauXDrp1þ/+- mice relative to Tau mice. Phosphorylated Tau levels were significantly reduced in TauXDrp1þ/+- mice relative to Tau mice. These findings suggest that a partial reduction of Drp1 decreases the levels of phosphorylated Tau, reduces mitochondrial dysfunction, and maintains mitochondrial dynamics, enhances mitochondrial biogenesis and synaptic activity in Tau mice.

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