Diseases caused by the aggregation of proteins are known as proteopathies, and they are primarily caused by aggregates in the following structures:
cytosol, e.g. Parkinsons and Huntingtons
nucleus, e.g. Spinocerebellar ataxia type 1 (SCA1)
endoplasmic reticulum (ER), (as seen with neuroserpin mutations that cause familial encephalopathy with neuroserpin inclusion bodies)
extracellularly excreted proteins, amyloid-beta in Alzheimers diseaseThere are two main avenues eukaryotic cells use to remove troublesome proteins or organelles:

ubiquitin–proteasome: protein ubiquitin along with enzymes is key for the degradation of many proteins that cause proteopathies including polyQ expansions and alpha-synucleins. Research indicates proteasome enzymes may not be able to correctly cleave these irregular proteins, which could possibly result in a more toxic species. This is the primary route cells use to degrade proteins.Decreased proteasome activity is consistent with models in which intracellular protein aggregates form. It is still unknown whether or not these aggregates are a cause or a result of neurodegeneration. autophagy–lysosome pathways: a form of programmed cell death (PCD), this becomes the favorable route when a protein is aggregate-prone meaning it is a poor proteasome substrate. This can be split into two forms of autophagy: macroautophagy and chaperone-mediated autophagy (CMA).macroautophagy is involved with nutrient recycling of macromolecules under conditions of starvation, certain apoptotic pathways, and if absent, leads to the formation of ubiquinated inclusions. Experiments in mice with neuronally confined macroautophagy-gene knockouts develop intraneuronal aggregates leading to neurodegeneration. chaperone-mediated autophagy defects may also lead to neurodegeneration.
Research has shown that mutant proteins bind to the CMA-pathway receptors on lysosomal membrane and in doing so block their own degradation as well as the degradation of other substrates. Membrane damage
Damage to the membranes of organelles by monomeric or oligomeric proteins could also contribute to these diseases. Alpha-synuclein can damage membranes by inducing membrane curvature, and cause extensive tubulation and vesiculation when incubated with artificial phospholipid vesicles.The tubes formed from these lipid vesicles consist of both micellar as well as bilayer tubes. Extensive induction of membrane curvature is deleterious to the cell and would eventually lead to cell death. Apart from tubular structures, alpha-synuclein can also form lipoprotein nanoparticles similar to apolipoproteins. Mitochondrial dysfunction
The most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial intermembrane space. Reactive oxygen species (ROS) are normal byproducts of mitochondrial respiratory chain activity. ROS concentration is mediated by mitochondrial antioxidants such as manganese superoxide dismutase (SOD2) and glutathione peroxidase. Over production of ROS (oxidative stress) is a central feature of all neurodegenerative disorders. In addition to the generation of ROS, mitochondria are also involved with life-sustaining functions including calcium homeostasis, PCD, mitochondrial fission and fusion, lipid concentration of the mitochondrial membranes, and the mitochondrial permeability transition.