Gene

Cell biology

Mitochondrial biogenesis

Neuroscience

Biology

Neuroinflammation

Cardiolipin

Neurodegeneration

Biochemistry

Immunology

Mitochondrial DNA

Membrane

TFAM

Microglia

mitochondrial fusion

Inflammation

Mitochondrion

Phospholipid

DNAJA3

Medicine

Disease

Pathology

Acta Pharmacologica Sinica

Both mitochondrial dysfunction and neuroinflammation are implicated in neurodegeneration and neurodegenerative diseases. Accumulating evidence shows multiple links between mitochondrial dysfunction and neuroinflammation. Mitochondrial-derived damage-associated molecular patterns (DAMPs) are recognized by immune receptors of microglia and aggravate neuroinflammation. On the other hand, inflammatory factors released by activated glial cells trigger an intracellular cascade, which regulates mitochondrial metabolism and function. The crosstalk between mitochondrial dysfunction and neuroinflammatory activation is a complex and dynamic process. There is strong evidence that mitochondrial dysfunction precedes neuroinflammation during the progression of diseases. Thus, an in-depth understanding of the specific molecular mechanisms associated with mitochondrial dysfunction and the progression of neuroinflammation in neurodegenerative diseases may contribute to the identification of new targets for the treatment of diseases. In this review, we describe in detail the DAMPs that induce or aggravate neuroinflammation in neurodegenerative diseases including mtDNA, mitochondrial unfolded protein response (mtUPR), mitochondrial reactive oxygen species (mtROS), adenosine triphosphate (ATP), transcription factor A mitochondria (TFAM), cardiolipin, cytochrome c , mitochondrial Ca 2+ and iron.

Mitochondrial-derived damage-associated molecular patterns amplify neuroinflammation in neurodegenerative diseases