Mitochondrial therapeutics in Alzheimer's disease and Parkinson's disease

Abstract

In neurons, mitochondria serve a wide variety of processes that are integral to their function and survival. It is, therefore, not surprising that evidence of mitochondrial dysfunction is observed across numerous neurodegenerative diseases. Alzheimer's disease and Parkinson's disease are two such diseases in which aberrant mitochondrial activity is proposed to contribute to pathogenesis. Current therapies for each disease target various mechanisms, but few, if any, directly target improved mitochondrial function. Recent discoveries pertaining to mitochondrial dynamics reveal that regulation of mitochondrial fission and fusion may play a key role in the pathogenesis of these diseases and consequently could be novel future therapeutic targets.

Figure 1

Synaptic function is dependent on proper trafficking of mitochondria to synapses. Mitochondrial trafficking down a neurite to a synapse can be promoted by increased fission (Drp1 or Fis1) or decreased fusion (Mfn1/2 or OPA1). Alterations in the levels of these proteins can lead to synaptic and mitochondrial dysfunction, neurodegeneration, and AD/PD pathogenesis. AD, Alzheimer's disease; Drp1, dynamin-related protein 1; Mfn, mitofusin; OPA1, optic atrophy 1; PD, Parkinson's disease.