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Molecular Dysfunctions of Mitochondria-Associated Membranes (MAMs) in Alzheimer's Disease

Fanny Eysert1, Paula Fernanda Kinoshita1,2, Arnaud Mary1

  • 1Université Côte d'Azur, INSERM, CNRS, Institut of Molecular and Cellular Pharmacology, Laboratory of Excellence DistalZ, Sophia-Antipolis, 06560 Valbonne, France.

International Journal of Molecular Sciences
|December 17, 2020
PubMed

Insights

Alzheimer's disease involves impaired communication between the endoplasmic reticulum (ER) and mitochondria. Targeting these mitochondria-associated membranes (MAMs) may offer new therapeutic strategies for cognitive decline.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is a neurodegenerative disorder causing cognitive decline.
  • Dysfunctional cellular signaling and communication between subcellular compartments contribute to AD.
  • Alterations in mitochondria-associated membranes (MAMs), the interface between ER and mitochondria, are implicated in AD.

Purpose of the Study:

  • To review the proteomic crosstalk between the ER and mitochondria.
  • To highlight the role of MAMs in ER and mitochondrial dysfunction in AD.
  • To discuss potential therapeutic strategies targeting MAMs for AD.

Main Methods:

  • Literature review of studies on ER-mitochondria crosstalk in AD.
  • Analysis of proteomic data related to MAMs.
  • Synthesis of current understanding of MAMs' role in AD pathogenesis.

Main Results:

  • MAMs are crucial for cellular functions including metabolism and calcium signaling, which are altered in AD.
  • Specific molecular components of MAMs contribute to mitochondrial and ER dysfunction in AD.
  • Dysregulation of MAMs impacts multiple cellular processes relevant to AD.

Conclusions:

  • MAMs represent a key nexus of cellular dysfunction in Alzheimer's disease.
  • Targeting MAMs offers a promising avenue for developing novel AD therapeutics.
  • Further research into MAMs' molecular components and functions is warranted for AD treatment.
Keywords:
APOEAPP-C-terminal fragments (APP-CTFs)Alzheimer’s disease (AD)Amyloid β peptide (Aβ)Endoplasmic Reticulum (ER)Mitochondria-Associated Membranes (MAMs)Unfolded Protein Response (UPR)calcium signalingcholesterolfatty acidlipidsmitochondriaphospholipidstauunfolded protein responseβ amyloid precursor protein (APP)

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